scholarly journals Metabolic responsiveness to training depends on insulin sensitivity and protein content of exosomes in insulin-resistant males

2021 ◽  
Vol 7 (41) ◽  
Author(s):  
Maria Apostolopoulou ◽  
Lucia Mastrototaro ◽  
Sonja Hartwig ◽  
Dominik Pesta ◽  
Klaus Straßburger ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Protein Content ◽  
Insulin Resistant

scholarly journals Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Sara M. Reyna ◽  
Puntip Tantiwong ◽  
Eugenio Cersosimo ◽  
Ralph A. DeFronzo ◽  
Apiradee Sriwijitkamol ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Protein Content ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Mitogen Activated Protein Kinase ◽  
Atherosclerotic Vascular Disease ◽  
Insulin Resistant ◽  
Erk Phosphorylation ◽  
Type 2 Diabetic

Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells.Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation.Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation.Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

Transthyretin contributes to insulin resistance and diminishes exercise-induced insulin sensitivity in obese mice by inhibiting AMPK activity in skeletal muscle

2021 ◽  
Author(s):  
Yingzi He ◽  
Ruojun Qiu ◽  
Beibei Wu ◽  
Weiwei Gui ◽  
Xihua Lin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Inhibitory Effect ◽  
Quadriceps Femoris ◽  
Treadmill Training ◽  
C2c12 Cells ◽  
Obese Mice ◽  
Insulin Resistant ◽  
Ampk Activity ◽  
Exercise Induced

Exercise improves obesity-induced insulin resistance and metabolic disorders via mechanisms that remain unclear. Here, we show that the levels of the hepatokine transthyretin (TTR) in circulation are elevated in insulin-resistant individuals including high-fat diet (HFD)-induced obese mice, db/db mice, and patients with metabolic syndrome. Liver Ttr mRNA and circulating TTR levels were reduced in mice by treadmill training, as was the TTR levels in quadriceps femoris muscle; however, AMPK signalling activity was enhanced. Transgenic overexpression of TTR or injection of purified TTR triggered insulin resistance in mice fed on regular chow (RC). Furthermore, TTR overexpression reduced the beneficial effects of exercise on insulin sensitivity in HFD-fed mice. TTR was internalized by muscle cells via the membrane receptor Grp78 and the internalization into the quadriceps femoris was reduced by treadmill training. The TTR/Grp78 combination in C2C12 cells was increased, whereas the AMPK activity of C2C12 cells was decreased as the TTR concentration rose. Additionally, Grp78 silencing prevented the TTR internalization and reversed its inhibitory effect on AMPK activity in C2C12 cells. Our study suggests that elevated circulating TTR may contribute to insulin resistance and counteract the exercise-induced insulin sensitivity improvement; the TTR suppression might be an adaptive response to exercise through enhancing AMPK activity in skeletal muscles.

scholarly journals Hepatokine ERAP1 impairs skeletal muscle insulin sensitivity via ADRB2/PKA pathway

2020 ◽  
Author(s):  
Feifan Guo ◽  
Yuguo Niu ◽  
Haizhou Jiang ◽  
Hanrui Yin ◽  
Fenfen Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Neutralizing Antibodies ◽  
Leptin Receptor ◽  
Whole Body ◽  
C2c12 Myotubes ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Sensitivity ◽  
Pka Pathway

Abstract The current study aimed to investigate the role of endoplasmic reticulum aminopeptidase 1 (ERAP1), a novel hepatokine, in whole-body glucose metabolism. Here, we found that hepatic ERAP1 levels were increased in insulin-resistant leptin-receptor-mutated (db/db) and high-fat diet (HFD)-fed mice. Consistently, hepatic ERAP1 overexpression attenuated skeletal muscle (SM) insulin sensitivity, whereas knockdown ameliorated SM insulin resistance. Furthermore, serum and hepatic ERAP1 levels were positively correlated, and recombinant mouse ERAP1 or conditioned medium with high ERAP1 content (CM-ERAP1) attenuated insulin signaling in C2C12 myotubes, and CM-ERAP1 or HFD-induced insulin resistance was blocked by ERAP1 neutralizing antibodies. Mechanistically, ERAP1 reduced ADRB2 expression and interrupted ADRB2-dependent signaling in C2C12 myotubes. Finally, ERAP1 inhibition via global knockout or the inhibitor thimerosal improved insulin sensitivity. Together, ERAP1 is a hepatokine that impairs SM and whole-body insulin sensitivity, and its inhibition might provide a therapeutic strategy for diabetes, particularly for those with SM insulin resistance.

scholarly journals Pioglitazone improves insulin resistance and decreases blood pressure in adult patients with congenital adrenal hyperplasia

2009 ◽  
Vol 161 (6) ◽  
pp. 887-894 ◽  
Author(s):  
Jeanne Margot Kroese ◽  
Christiaan F Mooij ◽  
Marinette van der Graaf ◽  
Ad R M M Hermus ◽  
Cees J Tack
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Body Fat ◽  
Matched Control ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Adrenal Hyperplasia ◽  
Insulin Resistant ◽  
Steroid Profiles

ContextPatients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity.ObjectivesTo assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles.DesignRandomized placebo controlled crossover trial.ParticipantsTwelve CAH patients and 12 body mass and age-matched control subjects.InterventionSixteen-week treatment with pioglitazone (45 mg/day) or placebo.Main outcome measureInsulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles.ResultsCAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P=0.000, GIR in controls 46.2±23.4 μmol/kg per min, P<0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0±13.6 vs 127.0±14.9 mmHg, P<0.001, diastolic: 72.8±11.5 vs 77.4±12.6 mmHg, P<0.001). No changes in body fat distribution, lipid, and steroid profiles were observed.ConclusionsCAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.

Abstract P149: A Large-scale Multi Ethnic Study of a Direct Measure of Insulin Sensitivity Demonstrates That South Asians are the Most Insulin Resistant Ethnic Group in the US

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Monica S Divakaruni ◽  
Fahim Abbasi ◽  
Manisha Desai ◽  
Cynthia A Lamendola ◽  
Latha Palaniappan ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Ethnic Group ◽  
Ethnic Groups ◽  
South Asian ◽  
Large Scale ◽  
South Asians ◽  
Insulin Resistant ◽  
The Us ◽  
Resistant Group ◽  
Direct Measures

Introduction: Insulin resistance (IR) is a known risk factor for heart disease. Few studies have compared race/ethnic differences in IR using ‘gold standard’ direct measures of insulin sensitivity. Methods: A total of 892 non-diabetic subjects (548 White, 106 South Asian, 103 East Asian, 86 Hispanic and 49 Black) underwent a 4-hour insulin suppression test (IST) as a part of various IR related studies at Stanford over the last ∼20 years. We used generalized estimating equations assuming an exchangeable correlation structure to determine the association between race/ethnicity and steady state plasma glucose (SSPG) derived from an IST, accounting for correlation of outcomes among subjects from the same study. We similarly determined whether differences in plasma triglyceride (TG) and high-density lipoprotein (HDL) levels among race/ethnic groups could be explained by differences in SSPG. All analyses were adjusted for age, sex, and BMI. Results: Significant differences among the race/ethnic groups in SSPG were observed (p <0.001). South Asians were the most insulin resistant group with a mean increase in SSPG of 38 mg/dL, compared to whites after controlling for age, sex, and BMI, a difference equivalent to ∼1/2 of the standard deviation of SSPG. East Asians were the next most resistant group (mean +33 mg/dl SSPG compared to whites) followed by Hispanics (+20 mg/dl), Whites, and Blacks (−7 mg/dl). South Asians were the only group with significantly higher TG (mean +1.16 fold, p=0.04) and lower HDL (−3.0 mg/dl, p=0.02) levels compared to whites but these differences were no longer evident after controlling for SSPG. In contrast, Blacks had significantly lower TG (mean 0.8 fold, p = 0.006) compared to whites, but this difference was not at all mitigated after adjusting for SSPG. Blacks also had no significant differences in HDL compared to whites. Conclusions: Direct measures of insulin sensitivity suggest that South Asians are the most insulin resistant race/ethnic group in the US even after adjusting for the principal determinants of IR. IR may be largely responsible for differences in TG and HDL observed between South Asian and other race/ethnic groups. The etiologies behind differences in insulin sensitivity across race/ethnic groups remain to be determined.

scholarly journals Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity

Life ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 127 ◽  
Author(s):  
Federica Vinciguerra ◽  
Andrea Tumminia ◽  
Roberto Baratta ◽  
Alfredo Ferro ◽  
Salvatore Alaimo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Children And Adolescents ◽  
Metabolic Phenotype ◽  
Sensitivity Index ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Insulin Resistant ◽  
Metabolically Healthy

Obesity represents a major risk factor for metabolic disorders, but some individuals, “metabolically healthy” (MHO), show less clinical evidence of these complications, in contrast to “metabolically unhealthy” (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment–insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

scholarly journals Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 502-512 ◽  
Author(s):  
Pieter de Groot ◽  
Torsten Scheithauer ◽  
Guido J Bakker ◽  
Andrei Prodan ◽  
Evgeni Levin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Bile Acids ◽  
Transit Time ◽  
Intestinal Transit ◽  
Faecal Microbiota ◽  
Intestinal Transit Time ◽  
Insulin Resistant

ObjectiveBariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.DesignSubjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.ResultsWe observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.ConclusionAllogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.Trial registration numberNTR4327.

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