Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient ...BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.展开更多
BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.展开更多
BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue...BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue,strenuous exercise,alcohol abuse,high carbohydrate intake and insulin injections are common triggers of paralysis.This article reports a case of severe TPP induced by insulin injection,elucidates the characteristics and pathogenesis of the disease,analyses the risk factors for triggering TPP,and hopefully provides more clinical data for TPP patients.CASE SUMMARY A 38-year-old Asian man presented to the emergency department with a oneweek history of limb weakness and worsening half-day.His medical history included poorly controlled type 2 diabetes and he had been switched to Aspart50 a week earlier.He was alert and oriented with upper extremity strength grade 3 and lower extremity strength grade 1.Emergency department tests showed hypokalemia of 1.6 mmol/L.The paramedics administered 1.5 g of potassium intravenously,followed by 4.0 g orally.Weakness in the arms and legs improved.He was referred to endocrinology where he was diagnosed with Graves'disease,with suboptimal control and insulin injections possibly causing TPP.We stopped his insulin and he was discharged with a potassium level of 4.0 mmol/L.CONCLUSION Insulin is a trigger for TPP and should be avoided in patients with hyperthyroidism.Early recognition and treatment of TPP is crucial,especially in patients presenting with hypokalemic periodic paralysis.展开更多
This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obe...This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.展开更多
Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin...Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.展开更多
Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in g...Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.展开更多
Background:Type 2 diabetes(T2D)accounts for the majority of diabetes incidences and remains a widespread global chronic disorder.Apart from early lifestyle changes,intervention options for T2D are mainly pharmaceutica...Background:Type 2 diabetes(T2D)accounts for the majority of diabetes incidences and remains a widespread global chronic disorder.Apart from early lifestyle changes,intervention options for T2D are mainly pharmaceutical.Methods:Repetitive transcranial magnetic stimulation(rTMS)has been approved by the FDA as a therapeutic intervention option for major depressive disorders,with further studies also indicating its role in energy metabolism and appetite.Considering its safe and non-invasive properties,we evaluated the effects of rTMS on systemic metabolism using T2D rats.Results:We observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10-day exposure.Improved systemic insulin sensitivity was main-tained after a 21-day treatment period,accompanied by modest yet significant weight loss.Circulating serum lipid levels,including those of cholesteryl ester,tryglyceride and ceramides,were also reduced following rTMS application.RNA-seq analyses fur-ther revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism.Altered expression of hypothalamic genes that are related to appetite regulation,neural activity and ether lipid metabolism were also implicated.Conclusion:In summary,our data report a positive impact of rTMS on systemic insu-lin sensitivity and weight management of T2D rats.The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.展开更多
BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which a...BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.展开更多
BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabet...BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.展开更多
Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan...Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.展开更多
BACKGROUND The possible existence of an acini–islet–acinar(AIA)reflex,involving mutual amylase and insulin interactions,was investigated in the current acute experiment on pigs.AIM To confirm the existence of an AIA...BACKGROUND The possible existence of an acini–islet–acinar(AIA)reflex,involving mutual amylase and insulin interactions,was investigated in the current acute experiment on pigs.AIM To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ.METHODS The study was performed on six pigs under general anesthesia.An intravenous glucose tolerance test was performed,with a bolus infusion of 50%glucose to the jugular vein,while amylase(5000 U/kg)or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate.RESULTS The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion,for>1 h.The intrapancreatic infusion of the vehicle(saline)did not have any effect on the time frame of insulin release.Infusion of 1%bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion,far beyond the glucose peak.CONCLUSION Intrapancreatic arterial infusion of amylase interrupted the integrated glucose–insulin interactions.This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ.展开更多
Diabetes mellitus remains a global health care challenge,promoting the search for innovative treatments.In vivo and in vitro studies have shown the potential benefits of ultrasound(US)on enhancing insulin release and ...Diabetes mellitus remains a global health care challenge,promoting the search for innovative treatments.In vivo and in vitro studies have shown the potential benefits of ultrasound(US)on enhancing insulin release and reactivating pancreaticβcell function.As a novel,nonpharmacological,noninvasive,and cost-effective approach,US therapy holds promise for stimulating pancreatic function and improving insulin secretion.This review explores recent findings on US therapy,focusing on low-intensity US(LIUS)and its effects on varying treatment parameters.Despite promising results,conflicting evidence highlights the need for further investigation through large-scale clinical trials to establish the therapeutic potential of US therapy and to optimize treatment regimens for effective diabetes management.The biological response to LIUS is complex and involves multiple cell types and pathways.The mechanisms triggering these effects require further exploration.A future engineering challenge lies in designing an experimental setup to control the US-induced mechanical phenomena,enabling the evaluation of biological effects with respect to parameters such as intensity,frequency,or duty cycle.展开更多
Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the pho...Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.展开更多
Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developi...Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.展开更多
AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation and progression of colorectal cancer.
BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skelet...BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.展开更多
BACKGROUND Insulin resistance and obesity present significant challenges in pediatric populations.Selenoprotein P1(SEPP1)serves as a biomarker for assessing selenium levels in the body.While its association with metab...BACKGROUND Insulin resistance and obesity present significant challenges in pediatric populations.Selenoprotein P1(SEPP1)serves as a biomarker for assessing selenium levels in the body.While its association with metabolic syndrome is established in adults,its relevance in children remains underexplored.AIM To ascertain SEPP1 blood levels in children and adolescents diagnosed with obesity and to assess its correlation with insulin resistance and adiposity indices.METHODS 170 children participated in this study,including 85 diagnosed with obesity and an equal number of healthy counterparts matched for age and sex.Each participant underwent a comprehensive medical evaluation,encompassing a detailed medical history,clinical examination,and anthropometric measurements like waist circumference and waist-to-height ratio.Furthermore,routine blood tests were conducted,including serum SEPP1,visceral adiposity index(VAI),and Homeostatic Model Assessment of Insulin Resistance(HOMA-IR)level.RESULTS Our findings revealed significantly lower serum SEPP1 levels in children with obesity compared to their healthy peers.Moreover,notable negative correlations were observed between serum SEPP1 levels and body mass index,VAI,and HOMA-IR.CONCLUSION The study suggests that SEPP1 could serve as a valuable predictor for insulin resistance among children and adolescents diagnosed with obesity.This highlights the potential utility of SEPP1 in pediatric metabolic health assessment and warrants further investigation.展开更多
Obesity,caused by excessive energy,leads to body weight gain and various diseases,including cognitive impairment.Current studies suggest that diet restriction such as optimal fasting and regular exercise are crucial f...Obesity,caused by excessive energy,leads to body weight gain and various diseases,including cognitive impairment.Current studies suggest that diet restriction such as optimal fasting and regular exercise are crucial for improving cognitive capacity.However,further exploration is needed to understand the specific mechanisms of high fat diet(HFD)-induced cognitive decline in obesity.In the present study,4-month-old mice were subjected to HFD feeding for 18 weeks,followed by aerobic exercise and high-intensity intermittent exercise,regular diet feeding,and intermittent fasting for 8 weeks,and then used to evaluate cognitive capacity,inflammation,compromised insulin signaling pathway,and apoptosis in hippocampal tissue,as well as AMPK/SIRT1 and TLR4 signal pathways.Obese mice revealed impaired cognitive capacity as compared with mice fed with regular diets.In contrast,aerobic exercise,high-intensity intermittent exercise,regular diet,and intermittent fasting could inhibit apoptosis caused by inflammation-mediated compromised insulin signaling pathway in hippocampal tissues through activating the AMPK/SIRT1 signal pathway and suppressing the TLR4 signal pathway,thereby rescuing the cognitive impairment of obese mice.Therefore,diet restriction and exercise interventions may play a positive role in reverting obesity-induced cognitive impairment.展开更多
With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic ...With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.展开更多
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2023-I2M-C&T-B-043National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015+1 种基金CAMS Innovation Fund for Medical Sciences,No.2021-1-12M-002Beijing Municipal Natural Science Foundation,No.M22014.
文摘BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
文摘BACKGROUND Thyrotoxic periodic paralysis(TPP)is an endocrine emergency caused by thyrotoxicosis,manifesting mainly as periodic myasthenia and hypokalemia,and posing a serious threat to the patient's health.Fatigue,strenuous exercise,alcohol abuse,high carbohydrate intake and insulin injections are common triggers of paralysis.This article reports a case of severe TPP induced by insulin injection,elucidates the characteristics and pathogenesis of the disease,analyses the risk factors for triggering TPP,and hopefully provides more clinical data for TPP patients.CASE SUMMARY A 38-year-old Asian man presented to the emergency department with a oneweek history of limb weakness and worsening half-day.His medical history included poorly controlled type 2 diabetes and he had been switched to Aspart50 a week earlier.He was alert and oriented with upper extremity strength grade 3 and lower extremity strength grade 1.Emergency department tests showed hypokalemia of 1.6 mmol/L.The paramedics administered 1.5 g of potassium intravenously,followed by 4.0 g orally.Weakness in the arms and legs improved.He was referred to endocrinology where he was diagnosed with Graves'disease,with suboptimal control and insulin injections possibly causing TPP.We stopped his insulin and he was discharged with a potassium level of 4.0 mmol/L.CONCLUSION Insulin is a trigger for TPP and should be avoided in patients with hyperthyroidism.Early recognition and treatment of TPP is crucial,especially in patients presenting with hypokalemic periodic paralysis.
文摘This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.
文摘Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.
文摘Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.
基金National Key Technologies Research and Development Program of China,Grant/Award Number:2020YFA0803701National Natural Science Foundation of China,Grant/Award Number:52107241,81973699 and 82274361CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-12M-1-052。
文摘Background:Type 2 diabetes(T2D)accounts for the majority of diabetes incidences and remains a widespread global chronic disorder.Apart from early lifestyle changes,intervention options for T2D are mainly pharmaceutical.Methods:Repetitive transcranial magnetic stimulation(rTMS)has been approved by the FDA as a therapeutic intervention option for major depressive disorders,with further studies also indicating its role in energy metabolism and appetite.Considering its safe and non-invasive properties,we evaluated the effects of rTMS on systemic metabolism using T2D rats.Results:We observed that rTMS improved glucose tolerance and insulin sensitivity in T2D rats after a 10-day exposure.Improved systemic insulin sensitivity was main-tained after a 21-day treatment period,accompanied by modest yet significant weight loss.Circulating serum lipid levels,including those of cholesteryl ester,tryglyceride and ceramides,were also reduced following rTMS application.RNA-seq analyses fur-ther revealed a changed expression profile of hepatic genes that are related to sterol production and fatty acid metabolism.Altered expression of hypothalamic genes that are related to appetite regulation,neural activity and ether lipid metabolism were also implicated.Conclusion:In summary,our data report a positive impact of rTMS on systemic insu-lin sensitivity and weight management of T2D rats.The underlying mechanisms via which rTMS regulates systemic metabolic parameters partially involve lipid utilization in the periphery as well as central regulation of energy intake and lipid metabolism.
文摘BACKGROUND Insulin autoimmune syndrome(IAS)is a severe manifestation of spontaneous hypoglycemia.It is characterized by elevated levels of immune-reactive insulin and highly potent insulin autoantibodies(IAAs),which are induced by endogenous insulin circulating in the bloodstream.It is distinguished by recurring instances of spontaneous hypoglycemia,the presence of IAA within the body,a substantial elevation in serum insulin levels,and an absence of prior exogenous insulin administration.Nevertheless,recent studies show that both conventional insulin and its analogs can induce IAS episodes,giving rise to the notion of nonclassical IAS.Therefore,more attention should be paid to these diseases.CASE SUMMARY In this case report,we present a rare case of non-classical IAS in an 83-year-old male patient who present with symptoms of a psychiatric disorder.Upon symptom onset,the patient exhibited Whipple's triad(including hypoglycemia,blood glucose level less than 2.8 mmol/L during onset,and rapid relief of hypoglycemic symptoms after glucose administration).Concurrently,his serum insulin level was significantly elevated,which contradicted his C-peptide levels.After a comprehensive examination,the patient was diagnosed with exogenous insulin autoimmune syndrome.Considering that the patient had type 2 diabetes mellitus and a history of exogenous insulin use before disease onset,it was presumed that non classical IAS was induced by this condition.The PubMed database was used to search for previous cases of IAS and non-classical IAS to analyze their characteristics and treatment approaches.CONCLUSION The occurrence of non-classical IAS is associated with exogenous insulin or its analogs,as well as with sulfhydryl drugs.Symptoms can be effectively alleviated through the discontinuation of relevant medications,administration of hormones or immunosuppressants,plasma exchange,and lifestyle adjustments.
基金Supported by The National Key R and D Program of China,No.2018YFC1314103The National Natural Science Foundation of China,No.81870563 and No.82270838.
文摘BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.
基金funded by the National Natural Science Foundation of China (32371341,31872674)the Scientific and Technologic Foundation of Jilin Province (20230202050NC)the Fundamental Research Funds for the Central Universities (CGZH202206)。
文摘Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.
文摘BACKGROUND The possible existence of an acini–islet–acinar(AIA)reflex,involving mutual amylase and insulin interactions,was investigated in the current acute experiment on pigs.AIM To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ.METHODS The study was performed on six pigs under general anesthesia.An intravenous glucose tolerance test was performed,with a bolus infusion of 50%glucose to the jugular vein,while amylase(5000 U/kg)or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate.RESULTS The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion,for>1 h.The intrapancreatic infusion of the vehicle(saline)did not have any effect on the time frame of insulin release.Infusion of 1%bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion,far beyond the glucose peak.CONCLUSION Intrapancreatic arterial infusion of amylase interrupted the integrated glucose–insulin interactions.This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ.
文摘Diabetes mellitus remains a global health care challenge,promoting the search for innovative treatments.In vivo and in vitro studies have shown the potential benefits of ultrasound(US)on enhancing insulin release and reactivating pancreaticβcell function.As a novel,nonpharmacological,noninvasive,and cost-effective approach,US therapy holds promise for stimulating pancreatic function and improving insulin secretion.This review explores recent findings on US therapy,focusing on low-intensity US(LIUS)and its effects on varying treatment parameters.Despite promising results,conflicting evidence highlights the need for further investigation through large-scale clinical trials to establish the therapeutic potential of US therapy and to optimize treatment regimens for effective diabetes management.The biological response to LIUS is complex and involves multiple cell types and pathways.The mechanisms triggering these effects require further exploration.A future engineering challenge lies in designing an experimental setup to control the US-induced mechanical phenomena,enabling the evaluation of biological effects with respect to parameters such as intensity,frequency,or duty cycle.
基金supported by the European Regional Development Funds-European Union(ERDF-EU),FATZHEIMER project(EU-LAC HEALTH 2020,16/T010131 to FRdF),“Una manera de hacer Europa”Ministerio de Economía,Industria y Competitividad,Gobierno de Espa?a,Programa Estatal de Investigación,Desarrollo e Innovación Orientada a los Retos de la Sociedad(RTC2019-007329-1 to FRdF)+2 种基金Consejería de Economía,Conocimiento y Universidad,Junta de Andalucía,Plan Andaluz de Investigación,Desarrollo e Innovación(P18TP-5194 to FRdF)Instituto de Salud CarlosⅢ(DTS22/00021 to FRdF)DMV(FI20/00227)holds a“PFIS’’predoctoral contract from the National System of Health,EU-ERDF-Instituto de Salud CarlosⅢ。
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.
文摘Diabetes mellitus(DM)and Alzheimer's disease(AD)are two major health concerns that have seen a rising prevalence worldwide.Recent studies have indicated a possible link between DM and an increased risk of developing AD.Insulin,while primarily known for its role in regulating blood sugar,also plays a vital role in protecting brain functions.Insulin resistance(IR),especially prevalent in type 2 diabetes,is believed to play a significant role in AD's development.When insulin signalling becomes dysfunctional,it can negatively affect various brain functions,making individuals more susceptible to AD's defining features,such as the buildup of beta-amyloid plaques and tau protein tangles.Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD.This review aims to explore the relationship between DM and AD,with a focus on the role of IR.It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR.Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.
文摘AIM: To investigate the roles of serum insulin, insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding proteins (IGFBPs) in the initiation and progression of colorectal cancer.
基金Supported by National Natural Science Foundation of China,No.32200944“Qing Lan”Project of Jiangsu Provincethe Jiangsu Research Institute of Sports Science Foundation,No.BM-2023-03.
文摘BACKGROUND Skeletal muscle handles about 80% of insulin-stimulated glucose uptake and become the major organ occurring insulin resistance(IR).Many studies have confirmed the interactions between macrophages and skeletal muscle regulated the inflammation and regeneration of skeletal muscle.However,despite of the decades of research,whether macrophages infiltration and polarization in skeletal muscle under high glucose(HG)milieus results in the development of IR is yet to be elucidated.C2C12 myoblasts are well-established and excellent model to study myogenic regulation and its responses to stimulation.Further exploration of macrophages'role in myoblasts IR and the dynamics of their infiltration and polarization is warranted.AIM To evaluate interactions between myoblasts and macrophages under HG,and its effects on inflammation and IR in skeletal muscle.METHODS We detected the polarization status of macrophages infiltrated to skeletal muscles of IR mice by hematoxylin and eosin and immunohistochemical staining.Then,we developed an in vitro co-culture system to study the interactions between myoblasts and macrophages under HG milieus.The effects of myoblasts on macrophages were explored through morphological observation,CCK-8 assay,Flow Cytometry,and enzyme-linked immunosorbent assay.The mediation of macrophages to myogenesis and insulin sensitivity were detected by morphological observation,CCK-8 assay,Immunofluorescence,and 2-NBDG assay.RESULTS The F4/80 and co-localization of F4/80 and CD86 increased,and the myofiber size decreased in IR group(P<0.01,g=6.26).Compared to Mc group,F4/80+CD86+CD206-cells,tumor necrosis factor-α(TNFα),inerleukin-1β(IL-1β)and IL-6 decreased,and IL-10 increased in McM group(P<0.01,g>0.8).In McM+HG group,F4/80+CD86+CD206-cells,monocyte chemoattractant protein 1,TNFα,IL-1βand IL-6 were increased,and F4/80+CD206+CD86-cells and IL-10 were decreased compared with Mc+HG group and McM group(P<0.01,g>0.8).Compered to M group,myotube area,myotube number and E-MHC were increased in MMc group(P<0.01,g>0.8).In MMc+HG group,myotube area,myotube number,E-MHC,GLUT4 and glucose uptake were decreased compared with M+HG group and MMc group(P<0.01,g>0.8).CONCLUSION Interactions between myoblasts and macrophages under HG milieus results in inflammation and IR,which support that the macrophage may serve as a promising therapeutic target for skeletal muscle atrophy and IR.
文摘BACKGROUND Insulin resistance and obesity present significant challenges in pediatric populations.Selenoprotein P1(SEPP1)serves as a biomarker for assessing selenium levels in the body.While its association with metabolic syndrome is established in adults,its relevance in children remains underexplored.AIM To ascertain SEPP1 blood levels in children and adolescents diagnosed with obesity and to assess its correlation with insulin resistance and adiposity indices.METHODS 170 children participated in this study,including 85 diagnosed with obesity and an equal number of healthy counterparts matched for age and sex.Each participant underwent a comprehensive medical evaluation,encompassing a detailed medical history,clinical examination,and anthropometric measurements like waist circumference and waist-to-height ratio.Furthermore,routine blood tests were conducted,including serum SEPP1,visceral adiposity index(VAI),and Homeostatic Model Assessment of Insulin Resistance(HOMA-IR)level.RESULTS Our findings revealed significantly lower serum SEPP1 levels in children with obesity compared to their healthy peers.Moreover,notable negative correlations were observed between serum SEPP1 levels and body mass index,VAI,and HOMA-IR.CONCLUSION The study suggests that SEPP1 could serve as a valuable predictor for insulin resistance among children and adolescents diagnosed with obesity.This highlights the potential utility of SEPP1 in pediatric metabolic health assessment and warrants further investigation.
基金supported by the National Natural Science Foundation of China(32471186,31771318)the 14^(th) Five-Year-Plan Advantageous and Characteristic Disciplines(Groups)of Colleges and Universities in Hubei Province for Exercise and Brain Science from Hubei Provincial Department of Education,and the Leading Talent Program Foundation from Wuhan Sports University to Ning Chen+3 种基金the National Natural Science Foundation of China(81701391)the Natural Science Foundation of Hubei Province(2023AFB700)Key Project of Scientific Research of Education Department of Hubei Province(D20234101)Young and Middle aged Scientific Research Team Project of Wuhan Sports University(21KT08)to Jingjing Fan.
文摘Obesity,caused by excessive energy,leads to body weight gain and various diseases,including cognitive impairment.Current studies suggest that diet restriction such as optimal fasting and regular exercise are crucial for improving cognitive capacity.However,further exploration is needed to understand the specific mechanisms of high fat diet(HFD)-induced cognitive decline in obesity.In the present study,4-month-old mice were subjected to HFD feeding for 18 weeks,followed by aerobic exercise and high-intensity intermittent exercise,regular diet feeding,and intermittent fasting for 8 weeks,and then used to evaluate cognitive capacity,inflammation,compromised insulin signaling pathway,and apoptosis in hippocampal tissue,as well as AMPK/SIRT1 and TLR4 signal pathways.Obese mice revealed impaired cognitive capacity as compared with mice fed with regular diets.In contrast,aerobic exercise,high-intensity intermittent exercise,regular diet,and intermittent fasting could inhibit apoptosis caused by inflammation-mediated compromised insulin signaling pathway in hippocampal tissues through activating the AMPK/SIRT1 signal pathway and suppressing the TLR4 signal pathway,thereby rescuing the cognitive impairment of obese mice.Therefore,diet restriction and exercise interventions may play a positive role in reverting obesity-induced cognitive impairment.
基金by National Natural Science Foundation of China(81803224)Young Scholars Program of Shandong University(2018WLJH33)to X.G.+3 种基金National Natural Science Foundation of China(81973031)Cheeloo Young Scholar Program of Shandong University(21320089963054)to H.W.Young Scholars Program of Shandong University(2018WLJH34)the Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology(LMDBKF-2019-05)to L.D.
文摘With the prevalence of obesity and obesity-related metabolic syndrome,such as insulin resistance in recent years,it is urgent to explore effective interventions to prevent the progression of obesity-related metabolic syndrome.Palmitoleic acid is a monounsaturated fatty acid that is available from dietary sources,mainly derived from marine products.P almitoleic acid plays a positive role in maintaining glucose homeostasis and reducing inflammation.However,it is still unknow the mechanism of palmitoleic acid in ameliorating insulin resistance.Here,we investigated the effects of palmitoleic acid on chow diet(CD)-fed and high-fat diet(HFD)-fed mice,which were fed CD or HFD for 12 weeks before administration.We administrated mice with BSA(control),oleic acid,or palmitoleic acid for 6 weeks on top of CD or HFD feeding.We found that palmitoleic acid only improved glucose homeostasis in HFD-fed obese mice by increasing glucose clearance and reducing HOMA-IR.Further study explored that palmitoleic acid changed the composition of gut microbiota by decreasing Firmicutes population and increasing Bacteroidetes population.In colon,palmitoleic acid increased intestinal tight junction integrity and reduced inflammation.Moreover,palmitoleic acid decreased macrophage infiltration in liver and adipose tissue and increase glucose uptake in adipose tissue.Diacylglycerol(DAG)in tissue(for example,liver)is found to positively correlated with HOMA-IR.HFD enhanced the levels of DAGs in liver but not in adipose tissue in this study.Palmitoleic acid did not reverse the high DAG levels induced by HFD in liver.Therefore,in HFD-fed mice,palmitoleic acid reduced insulin resistance by an independent-manner of DAGs.It might be associated with the beneficial effects of palmitoleic acid on altering the gut microbiota composition,improving of intestinal barrier function,and downregulating the inflammation in colon,liver,and adipose tissue.
