scholarly journals Oxidative phenotype induced by aerobic physical training prevents the obesity-linked insulin resistance without changes in gastrocnemius muscle ACE2-Angiotensin(1-7)-Mas axis

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bruno Vecchiatto ◽  
Rafael C. da Silva ◽  
Talita S. Higa ◽  
Cynthia R. Muller ◽  
Anna Laura V. Américo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Physical Training ◽  
Receptor Expression ◽  
Chow Diet ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor ◽  
Insulin Tolerance ◽  
Lower Body Weight ◽  
Maximal Speed ◽  
Oxidative Phenotype

Abstract Background We investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF). Methods Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks. Results Trained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL−1 120 min−1; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min−1, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO2 max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change. Conclusions The APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.

scholarly journals ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2020 ◽  
Author(s):  
Xiaobing Cui ◽  
Jia Fei ◽  
Sisi Chen ◽  
Gaylen L. Edwards ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
High Fat Diet ◽  
Peptide Yy ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Insulin Tolerance ◽  
Normal Chow

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1+/-) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Adar1+/- mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1+/- improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1+/- mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1+/- protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1+/- restored the increased ghrelin expression in stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induce obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion.

Exercise does not improve insulin resistance and mitochondrial characteristics together

2021 ◽  
Author(s):  
Amanda J Genders ◽  
Jujiao Kuang ◽  
Evelyn C Marin ◽  
Nicholas J Saner ◽  
Javier Botella ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Protein Expression ◽  
Respiratory Function ◽  
Citrate Synthase ◽  
Whole Body ◽  
Chow Diet ◽  
Mitochondrial Content ◽  
Insulin Tolerance ◽  
Mitochondrial Respiratory

The aim of this study was to investigate the relationship between mitochondrial content and respiratory function and whole-body insulin resistance in high fat diet (HFD) fed rats. Male Wistar rats were given either a chow diet or a HFD for 12 weeks. After four weeks of the dietary intervention, half of the rats in each group began eight weeks of interval training. In vivo glucose and insulin tolerance were assessed. Mitochondrial respiratory function was assessed in permeabilised soleus and white gastrocnemius (WG) muscles. Mitochondrial content was determined by measurement of citrate synthase (CS) activity and protein expression of components of the electron transport system (ETS). We found HFD rats had impaired glucose and insulin tolerance but increased mitochondrial respiratory function and increased protein expression of components of the ETS. This was accompanied by an increase in CS activity in WG. Exercise training improved glucose and insulin tolerance in the HFD rats. Mitochondrial respiratory function was increased with exercise training in the chow fed animals in soleus muscle. This exercise effect was absent in the HFD animals. In conclusion, exercise training improved insulin resistance in HFD rats, but without changes in mitochondrial respiratory function and content. The lack of an association between mitochondrial characteristics and whole-body insulin resistance was reinforced by the absence of strong correlations between these measures. Our results suggest that improvements in mitochondrial respiratory function and content are not responsible for improvements of whole-body insulin resistance in HFD rats.

Angiotensin-(1–7) prevents systemic hypertension, attenuates oxidative stress and tubulointerstitial fibrosis, and normalizes renal angiotensin-converting enzyme 2 and Mas receptor expression in diabetic mice

2015 ◽  
Vol 128 (10) ◽  
pp. 649-663 ◽  
Author(s):  
Yixuan Shi ◽  
Chao-Sheng Lo ◽  
Ranjit Padda ◽  
Shaaban Abdo ◽  
Isabelle Chenier ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Converting Enzyme ◽  
Renal Injury ◽  
Receptor Expression ◽  
Systemic Hypertension ◽  
Converting Enzyme ◽  
Diabetic Mice ◽  
Angiotensin Converting Enzyme 2 ◽  
Mas Receptor

In summary, our data indicate an important role of Ang-(1–7) in inhibiting intrarenal oxidative stress and subsequent prevention of the development of hypertension and renal injury in diabetic mice.

scholarly journals High-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice

2015 ◽  
Vol 308 (7) ◽  
pp. E573-E582 ◽  
Author(s):  
Rockann E. Mosser ◽  
Matthew F. Maulis ◽  
Valentine S. Moullé ◽  
Jennifer C. Dunn ◽  
Bethany A. Carboneau ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Proliferation ◽  
High Fat Diet ◽  
Cell Mass ◽  
Chow Diet ◽  
High Fat ◽  
Β Cell ◽  
Peripheral Insulin Resistance ◽  
Insulin Tolerance

Both short- (1 wk) and long-term (2–12 mo) high-fat diet (HFD) studies reveal enhanced β-cell mass due to increased β-cell proliferation. β-Cell proliferation following HFD has been postulated to occur in response to insulin resistance; however, whether HFD can induce β-cell proliferation independent of insulin resistance has been controversial. To examine the kinetics of HFD-induced β-cell proliferation and its correlation with insulin resistance, we placed 8-wk-old male C57Bl/6J mice on HFD for different lengths of time and assayed the following: glucose tolerance, insulin secretion in response to glucose, insulin tolerance, β-cell mass, and β-cell proliferation. We found that β-cell proliferation was significantly increased after only 3 days of HFD feeding, weeks before an increase in β-cell mass or peripheral insulin resistance was detected. These results were confirmed by hyperinsulinemic euglycemic clamps and measurements of α-hydroxybutyrate, a plasma biomarker of insulin resistance in humans. An increase in expression of key islet-proliferative genes was found in isolated islets from 1-wk HFD-fed mice compared with chow diet (CD)-fed mice. These data indicate that short-term HFD feeding enhances β-cell proliferation before insulin resistance becomes apparent.

scholarly journals Protective effects of calorie restriction on insulin resistance and islets function in STZ-induced type 2 diabetes rats

2020 ◽  
Author(s):  
Li Zhang ◽  
Ying-juan Huang ◽  
Jia-pan Sun ◽  
Ting-ying Zhang ◽  
Tao-li Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Glucose Uptake ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Chow Diet ◽  
Protective Effects ◽  
Insulin Tolerance ◽  
Calorie Diet

Abstract Background Caloric restriction (CR), as the only approved scientific method that can retard aging, has become more and more attractive in the treatment of type 2 diabetes mellitus (T2DM) due to increasingly common high calorie diet and sedentary lifestyle. This study aimed to evaluate its role in T2DM treatment and further explored the potential molecular mechanism.Methods A total of 60 male SD rats were used in this study. Diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30mg/kg). Subsequently, the diabetic rats were fed ab libitum of 28g/day (diabetic control) or 20g/day (30% CR regimen) with HFD for 20 weeks. Meanwhile, normal rats had free standard chow diet served as vehicle control. Body mass, plasma glucose, and lipid profile were monitored. After diabetes-related functional tests being done, rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle were determined. Liver and pancreas were prepared for histopathology and histochemical evaluations, and western blotting and immunofluorescence were applied to detect alterations in AKT/AS160/GLUT4 signaling. Results 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity, thus protected islets secretion, retarding the exhaustion of islets function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and HOMA-IR. However, glucose uptake in skeletal muscle was not significantly improved, and the up-regulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR attenuated gradually over time. However, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion 30% CR could protect islets function from hyperglycemia and dyslipidemia, and improve insulin resistance with probable mechanism related to the up-regulation of AKT/AS160/GLUT4 signaling.

Swimming training improves the vasodilator effect of angiotensin-(1–7) in the aorta of spontaneously hypertensive rat

2011 ◽  
Vol 111 (5) ◽  
pp. 1272-1277 ◽  
Author(s):  
Denise M. R. Silva ◽  
Ary Gomes-Filho ◽  
Vania C. Olivon ◽  
Tassia M. S. Santos ◽  
Lenice K. Becker ◽  
...  
Keyword(s):  
Physical Training ◽  
Spontaneously Hypertensive Rat ◽  
Critical Role ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Swimming Training ◽  
Vascular Effects ◽  
Vasodilator Effect ◽  
Vasodilator Response ◽  
Mas Receptor

Introduction: endothelial dysfunction plays a critical role in the pathogenesis of hypertension. It is well established that physical training has beneficial effects on the cardiovascular system. We recently reported that angiotensin-(1–7) [Ang-(1–7)] concentration and the Mas receptor expression is increased in the left ventricle of trained spontaneous hypertensive rats (SHR). The vascular effects of Ang-(1–7) in trained animals remain so far unknown. In the present study we investigated the effects of physical training on the vasodilator effect of Ang-(1–7) in the aorta of SHR. Methodology: normotensive Wistar rats and SHR were subjected to an 8-wk period of 5% overload of body weight swimming training. Changes in isometric tension were recorded on myograph. Western blot was used to investigate Ang-(1–7) receptors expression. Results: in aortas from normotensive rats Ang-(1–7) and ACh induced a concentration-dependent vasodilator effect, which was not modified by the physical training. Vessels from SHR had an impaired vasodilator response to Ang-(1–7) and ACh. The swimming training strongly potentiated the vasodilator effect induced by Ang-(1–7) in SHR, but did not modify the effect of ACh. Interestingly, Mas receptor protein expression was substantially increased by physical training in SHR. In trained SHR, the vasodilator effect of Ang-(1–7) was abrogated by removal of the endothelium and by the selective Ang-(1–7) receptor antagonists A-779 and d-Pro7-Ang-(1–7). l-NAME decreased Ang-(1–7) vasodilator response and indomethacin abolished the remaining dilatory response. Conclusion: physical training increased Mas receptors expression in SHR aortas, thereby improving the vasodilator effect of Ang-(1–7) through an endothelium-dependent mechanism involving nitric oxide and prostacyclin.

scholarly journals Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophie Jacques ◽  
Arash Arjomand ◽  
Hélène Perée ◽  
Patrick Collins ◽  
Alice Mayer ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Damage ◽  
Chow Diet ◽  
Serum Triglycerides ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.

scholarly journals Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ionel Sandovici ◽  
Constanze M. Hammerle ◽  
Sam Virtue ◽  
Yurena Vivas-Garcia ◽  
Adriana Izquierdo-Lahuerta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Homeostasis ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Chow Diet ◽  
Genome Wide Association Studies ◽  
Cell Plasticity ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

AbstractWhen exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.

Effect of a Polyphenol-Rich Extract from Aloe vera Gel on Experimentally Induced Insulin Resistance in Mice

2007 ◽  
Vol 35 (06) ◽  
pp. 1037-1046 ◽  
Author(s):  
Yolanda Y. Pérez ◽  
Enrique Jiménez-Ferrer ◽  
Alejandro Zamilpa ◽  
Marcelino Hernández-Valencia ◽  
Francisco J. Alarcón-Aguilar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Aloe Vera ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Glucose Levels ◽  
Insulin Tolerance ◽  
Aloe Vera Gel ◽  
Experimentally Induced

Insulin resistance, which precedes type 2 diabetes mellitus (T2DM), is a widespread pathology associated with the metabolic syndrome, myocardial ischemia, and hypertension. Finding an adequate treatment for this pathology is an important goal in medicine. The purpose of the present research was to investigate the effect of an extract from Aloe vera gel containing a high concentration of polyphenols on experimentally induced insulin resistance in mice. A polyphenol-rich Aloe vera extract (350 mg/kg) with known concentrations of aloin (181.7 mg/g) and aloe-emodin (3.6 mg/g) was administered orally for a period of 4 weeks to insulin resistant ICR mice. Pioglitazone (50 mg/kg) and bi-distilled water were used as positive and negative controls respectively. Body weight, food intake, and plasma concentrations of insulin and glucose were measured and insulin tolerance tests were performed. The insulin resistance value was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. Results showed that the polyphenol-rich extract from Aloe vera was able to decrease significantly both body weight ( p < 0.008) and blood glucose levels ( p < 0.005) and to protect animals against unfavorable results on HOMA-IR, which was observed in the negative control group. The highest glucose levels during the insulin tolerance curve test were in the negative control group when compared to the Aloe vera extract and pioglitazone treated mice ( p < 0.05). In conclusion, Aloe vera gel could be effective for the control of insulin resistance.

Sign in / Sign up

Export Citation Format

Share Document