Ghrelin regulates insulin resistance by targeting insulin-like growth factor-1 receptor via miR-455-5p in hepatic cells

Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.

Palmitoleic acid on top of HFD ameliorates insulin resistance independent of diacylglycerols and alters gut microbiota in C57BL/6J mice

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.

Dynamics in the Prevalence of Insulin Resistance between 2005 and 2023 in Type 2 Diabetics in South Kivu in the East of the Democratic Republic of Congo: Cross-Sectional Studies

Aim: Sub-Saharan Africa is undergoing an epidemiological transition responsible for a change in the metabolic profile in favour of insulin resistance. The aim of this study was to assess the dynamics of the prevalence of insulin resistance and associated risk factors in diabetic patients in the Democratic Republic of Congo between 2005 and 2023. Method: We measured fasting blood glucose and insulin levels and looked for metabolic syndrome parameters (2009 criteria) in type 2 diabetes patients in 2005-2008 (n = 176) and in 2018-2023 (n = 303). The HOMA model was used to measure insulin sensitivity and islet β-cell secretory function. Results: Between 2005 and 2013, the trend was towards an increase in the prevalence of insulin resistance (from 13.1% to 50.8%;p Conclusion: This present study shows an increase in insulin resistance in Congolese urban areas and a persistence of atypical diabetes mellitus in Congolese rural areas, confirming the particularity of the pathophysiology of the disease in African areas currently influenced by the epidemiological transition. Further studies using an appropriate methodology are required.

Effects of vitamin family members on insulin resistance and diabetes complications

The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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.

Mapping the global research landscape on nonalcoholic fatty liver disease and insulin resistance:A visualization and bibliometric study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a liver condition that is prevalent worldwide and associated with significant health risks and economic burdens.As it has been linked to insulin resistance(IR),this study aimed to perform a bibliometric analysis and visually represent the scientific literature on IR and NAFLD.AIM To map the research landscape to underscore critical areas of focus,influential studies,and future directions of NAFLD and IR.METHODS This study conducted a bibliometric analysis of the literature on IR and NAFLD indexed in the SciVerse Scopus database from 1999 to 2022.The search strategy used terms from the literature and medical subject headings,focusing on terms related to IR and NAFLD.VOSviewer software was used to visualize research trends,collaborations,and key thematic areas.The analysis examined publication type,annual research output,contributing countries and institutions,funding agencies,journal impact factors,citation patterns,and highly cited references.RESULTS This analysis identified 23124 documents on NAFLD,revealing a significant increase in the number of publications between 1999 and 2022.The search retrieved 715 papers on IR and NAFLD,including 573(80.14%)articles and 88(12.31%)reviews.The most productive countries were China(n=134;18.74%),the United States(n=122;17.06%),Italy(n=97;13.57%),and Japan(n=41;5.73%).The leading institutions included the Universitàdegli Studi di Torino,Italy(n=29;4.06%),and the Consiglio Nazionale delle Ricerche,Italy(n=19;2.66%).The top funding agencies were the National Institute of Diabetes and Digestive and Kidney Diseases in the United States(n=48;6.71%),and the National Natural Science Foundation of China(n=37;5.17%).The most active journals in this field were Hepatology(27 publications),the Journal of Hepatology(17 publications),and the Journal of Clinical Endocrinology and Metabolism(13 publications).The main research hotspots were“therapeutic approaches for IR and NAFLD”and“inflammatory and high-fat diet impacts on NAFLD”.CONCLUSION This is the first bibliometric analysis to examine the relationship between IR and NAFLD.In response to the escalating global health challenge of NAFLD,this research highlights an urgent need for a better understanding of this condition and for the development of intervention strategies.Policymakers need to prioritize and address the increasing prevalence of NAFLD.

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance

BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.METHODS To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with LGZG.The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests.Using a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic steatosis.It effectively controlled blood glucose and food intake while protecting islet cells.Metabolite analysis revealed significant differences between the HFD and HFDLGZG groups.LGZG intervention reduced branched-chain amino acid levels.Levels of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased significantly.IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by qRT-PCR.CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR.LGZG may activate S6K1 via metabolic pathways.These findings lay the groundwork for the potential of LGZG as an IR treatment.

KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and AD.KAT7 is a histone acetyltransferase that participates in the modulation of various genes.AIM To determine the effects of KAT7 on insulin patients with AD.METHODS APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,respectively.An in vitro model of AD was established by Aβstimulation.Insulin resistance was induced by chronic stimulation with high insulin levels.The expression of microtubule-associated protein 2(MAP2)was assessed using immunofluorescence.The protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western blotting.Accumulation of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative stress.Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,respectively.Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A.RESULTS KAT7 expression was suppressed in the AD mice.Overexpression of KAT7 decreased Aβaccumulation and MAP2 expression in AD brains.KAT7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal apoptosis.KAT7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of DYRK1A.KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A.HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion.CONCLUSION We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation.Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.

Association between cardiorespiratory fitness level and insulin resistance in adolescents with various obesity categories

BACKGROUND An association between cardiorespiratory fitness(CRF)and insulin resistance in obese adolescents,especially in those with various obesity categories,has not been systematically studied.There is a lack of knowledge about the effects of CRF on insulin resistance in severely obese adolescents,despite their continuous rise.AIM To investigate the association between CRF and insulin resistance in obese adolescents,with special emphasis on severely obese adolescents.METHODS We performed a prospective,cross-sectional study that included 200 pubertal adolescents,10 years to 18 years of age,who were referred to a tertiary care center due to obesity.According to body mass index(BMI),adolescents were classified as mildly obese(BMI 100% to 120% of the 95^(th)percentile for age and sex)or severely obese(BMI≥120% of the 95^(th)percentile for age and sex or≥35 kg/m^(2),whichever was lower).Participant body composition was assessed by bioelectrical impedance analysis.A homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.Maximal oxygen uptake(VO_(2)max)was determined from submaximal treadmill exercise test.CRF was expressed as VO_(2)max scaled by total body weight(TBW)(mL/min/kg TBW)or by fat free mass(FFM)(mL/min/kg FFM),and then categorized as poor,intermediate,or good,according to VO_(2)max terciles.Data were analyzed by statistical software package SPSS(IBM SPSS Statistics for Windows,Version 24.0).P<0.05 was considered statistically significant.RESULTS A weak negative correlation between CRF and HOMA-IR was found[Spearman’s rank correlation coefficient(rs)=-0.28,P<0.01 for CRF_(TBW);(r_(s))=-0.21,P<0.01 for CRF_(FFM)].One-way analysis of variance(ANOVA)revealed a significant main effect of CRF on HOMA-IR[F(2200)=6.840,P=0.001 for CRF_(TBW);F_((2200))=3.883,P=0.022 for CRF_(FFM)].Subsequent analyses showed that obese adolescents with poor CRF had higher HOMA-IR than obese adolescents with good CRF(P=0.001 for CRF_(TBW);P=0.018 for CRF_(FFM)).Two-way ANOVA with Bonferroni correction confirmed significant effect of interaction of CRF level and obesity category on HOMA-IR[F_((2200))=3.292,P=0.039 for CRF_(TBW)].Severely obese adolescents had higher HOMA-IR than those who were mildly obese,with either good or poor CRF.However,HOMA-IR did not differ between severely obese adolescents with good and mildly obese adolescents with poor CRF.CONCLUSION CRF is an important determinant of insulin resistance in obese adolescents,regardless of obesity category.Therefore,CRF assessment should be a part of diagnostic procedure,and its improvement should be a therapeutic goal.

Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic steatosis.As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease globally.Huangqin decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including NAFLD.However,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.AIM To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of action.METHODS High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action.Phytochemicals in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin resistance.In vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 cells.In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.

Exploration of the molecular mechanism of Qishen decoction in regulating miR-495/FTO pathway mediated macrophage polarization to improve insulin resistance therapy of type 2 diabetes

Objective:To observe the effect of Qishen decoction on macrophage polarization mediated by miR-495/FTO signaling pathway,and to clarify the molecular mechanism of Qishen decoction in improving insulin resistance in the treatment of type 2 diabetes.Methods:THP-1 was induced to differentiate macrophages with phorbol ester.It was divided into the control group,the model group,the Qishen decoction group,the miR-495 inhibitor group,and the Qishen decoction+miR-495 inhibitor group.Except for the control group,the remaining groups were stimulated with 30 mmol/L glucose to construct a macrophage polarization model,and corresponding drugs were given for intervention.Cells were collected from each group for 24 hours and the content of inflammatory factors(IL-6,IL-1β,IL-4,and IL-10)were detected using enzyme-linked immunosorbent assay.The expression of macrophage polarization marker molecules,miR-495,and FTO were detected by flow cytometry,qPCR,and Western blot to detect.Results:Compared with the control group,there was no significant change in the activity of macrophages in the control serum,Qishen decoction containing serum,and miR-495 inhibitor transfected serum,and the difference was not statistically significant(P>0.05).In addition,compared to the control group,the content of IL-6 and IL-1β,the expression levels of CD68,iNOS,COX-2,miR-495,and the ratio of CD68/CD206,were significantly increased(P<0.01).While the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly reduced(P<0.01).Compared with the model group,the QiShen decoction significantly reduced the contents of IL-6 and IL-1β,and the expression levels of CD68,iNOS,COX-2,and miR-495,as well as the ratio of CD68/CD206,while the content of IL-4 and IL-10,as well as the expression of CD206,Arg-1,YM-1,and FTO were significantly increased(P<0.01).Conclusion:Qishen decoction upregulate the expression of FTO to promote M2 type polarization of macrophages,thereby inhibiting inflammation and improving insulin resistance by inhibiting the expression of miR-495.

Simiao Wan alleviates obesity-associated insulin resistance via PKCε/IRS-1/PI3K/Akt signaling pathway based on network pharmacology analysis and experimental validation

Background:The purpose of the study was to investigatethe active ingredients and potential biochemicalmechanisms of Simiao Wan(SMW)in obesity-associated insulin resistance.Methods:An integrated network pharmacology method to screen the active compoundsand candidate targets,construct the protein-protein-interaction network,and ingredients-targets-pathways network was constructed for topological analysis to identify core targets and main ingredients.To find the possible signaling pathways,enrichment analysis was performed.Further,a model of insulin resistance in HL-7702 cells was established to verify the impact of SMW and the regulatory processes.Results:An overall of 63 active components and 151 candidate targets were obtained,in which flavonoids were the main ingredients.Enrichment analysis indicated that the PI3K-Akt signaling pathway was the potential pathway regulated by SMW in obesity-associated insulin resistance treatment.The result showed that SMW could significantly ameliorate insulin sensitivity,increase glucose synthesis and glucose utilization and reduce intracellular lipids accumulation in hepatocytes.Also,SMW inhibited diacylglycerols accumulation-induced PKCεactivity and decreased its translocation to the membrane.Conclusion:SMW ameliorated obesity-associated insulin resistance through PKCε/IRS-1/PI3K/Akt signaling axis in hepatocytes,providing a new strategy for metabolic disease treatment.

Role of selenium in type 2 diabetes,insulin resistance and insulin secretion

Selenium is a trace mineral essential for life that acts physiologically through selenoproteins.Among other actions,the endogenous antioxidant selenoprotein glutathione peroxidase and the selenium transporter in blood,selenoprotein P,seem to play an important role in type 2 diabetes mellitus and insulin resistance by weakening the insulin signaling cascade through different mechanisms.Recent findings also suggest that selenoproteins also affect insulin biosynthesis and insulin secretion.This review discussed the role of selenium in type 2 diabetes and the complex interplay between selenoproteins and insulin pathways.

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance

BACKGROUND Type 2 diabetes mellitus(T2DM)is a chronic metabolic disease featured by insulin resistance(IR)and decreased insulin secretion.Currently,vitamin D deficiency is found in most patients with T2DM,but the relationship between vitamin D and IR in T2DM patients requires further investigation.AIM To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM.METHODS Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed.Based on the diagnostic criteria of IR,the patients were divided into a resistance group(n=100)and a non-resistance group(n=62).Subsequently,patients in the resistance group were subdivided to a conventional group(n=44)or a joint group(n=56)according to the treatment regimens.Logistic regression was carried out to analyze the risk factors of IR in T2DM patients.The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment.RESULTS Notable differences were observed in age and body mass index(BMI)between the resistance group and the non-resistance group(both P<0.05).The resistance group exhibited a lower 25-hydroxyvitamin D_(3)(25(OH)D_(3))level,as well as notably higher levels of 2-h postprandial blood glucose(2hPG),fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)than the non-resistance group(all P<0.0001).Additionally,the resistance group demonstrated a higher triglyceride(TG)level but a lower high-density lipoprotein-cholesterol(HDL-C)level than the non-resistance group(all P<0.0001).The BMI,TG,HDL-C,25(OH)D_(3),2hPG,and HbA1c were found to be risk factors of IR.Moreover,the posttreatment changes in levels of 25(OH)D_(3),2hPG,FBG and HbA1c,as well as TG,total cholesterol,and HDL-C in the joint group were more significant than those in the conventional group(all P<0.05).CONCLUSION Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the noninsulin resistant group.Logistic regression analysis revealed that 25(OH)D_(3)is an independent risk factor influencing IR.Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

miRNA-103: Molecular link between insulin resistance and nonalcoholic fatty liver disease

AIM: To investigate the associations between miRNA-103(mi R-103) and insulin resistance and nonalcoholic fatty liver disease(NAFLD).METHODS: Serum samples were collected from 50 NAFLD patients who were overweight or obese(NAFLD group) and from 30 healthy subjects who served as controls(normal control group). Quantitative polymerasechain reaction was used to detect expression of mi R-103. Fasting plasma glucose, fasting insulin, and triglyceride(TG) levels were measured. Homeostasis model assessment was used to evaluate basal insulin resistance(HOMA-IR). Patient height and weight were measured to calculate body mass index(BMI).RESULTS: Compared with the normal control group, higher serum levels of mi R-103 were expressed in the NAFLD group(8.18 ± 0.73 vs 4.23 ± 0.81, P = 0.000). When P = 0.01(bilateral), mi R-103 was positively correlated with HOMA-IR(r = 0.881), TG(r = 0.774) and BMI(r = 0.878), respectively. mi R-103, TG and BMI were all independent factors for HOMAIR(β = 0.438/0.657/0.251, P = 0.000/0.007/0.001). mi R-103, TG, BMI and HOMA-IR were all risk factors for NAFLD(odds ratio = 2.411/16.196/1.574/19.11, P = 0.009/0.022/0.01/0.014).CONCLUSION: mi R-103 is involved in insulin resistance and NAFLD, and may be a molecular link between insulin resistance and NAFLD and a therapeutic target for these disorders.

Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indicates that HCV-associated insulin resistance may cause(1) hepatic steatosis;(2) resistance to anti-viral treatment;(3) hepatic f ibrosis and esophageal varices;(4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma;and(5) extrahepatic manifestations.Thus,HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection.Although the risk of insulin resistance in HCV-infected patients has been documented,therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established.In addition,mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance.In order to ameliorate HCV-associated insulin resistance and its complications,the eff icacy of the following interventions is discussed:a late evening snack,coffee consumption,dietary iron restriction,phlebotomy,and zinc supplements.Little is known regarding the effect of anti-diabetic agents on HCV infection,however,a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported.On the other hand,insulin-sensitizing agents are reported to improve sustained virologic response rates.In this review,we summarize distinctive complications of,and therapeutic strategies for,HCVassociated insulin resistance.Furthermore,we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCVassociated insulin resistance.

Hepatitis C virus infection and insulin resistance

Approximately 170 million people worldwide are chronically infected with hepatitis C virus(HCV).Chronic HCV infection is the leading cause for the development of liver fibrosis,cirrhosis,hepatocellular carcinoma(HCC)and is the primary cause for liver transplantation in the western world.Insulin resistance is one of the pathological features in patients with HCV infection and often leads to development of typeⅡdiabetes.Insulin resistance plays an important role in the development of various complications associated with HCV infection.Recent evidence indicates that HCV associated insulin resistance may result in hepatic fibrosis,steatosis,HCC and resistance to anti-viral treatment.Thus,HCV associated insulin resistance is a therapeutic target at any stage of HCV infection.HCV modulates normal cellular gene expression and interferes with the insulin signaling pathway.Various mechanisms have been proposed in regard to HCV mediated insulin resistance,involving up regulation of inflammatory cytokines,like tumor necrosis factor-α,phosphorylation of insulin-receptor substrate-1,Akt,up-regulation of gluconeogenic genes like glucose 6 phosphatase,phosphoenolpyruvate carboxykinase 2,and accumulation of lipid droplets.In this review,we summarize the available information on how HCV infection interferes with insulin signaling pathways resulting in insulin resistance.

Interaction of IFNL3 with insulin resistance,steatosis and lipid metabolism in chronic hepatitis C virus infection

Metabolic changes are inextricably linked to chronic hepatitis C(CHC).Recently polymorphisms in the IFNL3(IL28B)region have been shown to be strongly associated with spontaneous and treatment induced recovery from hepatitis C virus(HCV)infection.Further,circumstantial evidence suggests a link between IFNL3single nucleotide polymorphisms and lipid metabolism,steatosis and insulin resistance in CHC.The emerging picture suggests that the responder genotypes of IFNL3polymorphisms are associated with a higher serum lipid profile,and less frequent steatosis and insulin resistance.This review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression.