scholarly journals Selective Inactivation of c-Jun NH2-Terminal Kinase in Adipose Tissue Protects Against Diet-Induced Obesity and Improves Insulin Sensitivity in Both Liver and Skeletal Muscle in Mice

Diabetes ◽  
2011 ◽  
Vol 60 (2) ◽  
pp. 486-495 ◽  
Author(s):  
X. Zhang ◽  
A. Xu ◽  
S. K. Chung ◽  
J. H. B. Cresser ◽  
G. Sweeney ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Diet Induced Obesity

Interactions between insulin and exercise

2021 ◽  
Vol 478 (21) ◽  
pp. 3827-3846
Author(s):  
Erik A. Richter ◽  
Lykke Sylow ◽  
Mark Hargreaves
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Regular Exercise ◽  
Fuel Storage ◽  
Storage Effects ◽  
Glucose Storage ◽  
Glycogen Stores

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

DPP4 deletion in adipose tissue improves hepatic insulin sensitivity in diet-induced obesity

2020 ◽  
Vol 318 (5) ◽  
pp. E590-E599 ◽  
Author(s):  
Tania Romacho ◽  
Henrike Sell ◽  
Ira Indrakusuma ◽  
Diana Roehrborn ◽  
Tamara R. Castañeda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Hepatic Insulin Sensitivity ◽  
Dipeptidyl Peptidase 4 ◽  
Diet Induced Obesity ◽  
Hepatic Fat ◽  
Igf Binding ◽  
Igf Binding Protein

Besides a therapeutic target for type 2 diabetes, dipeptidyl peptidase 4 (DPP4) is an adipokine potentially upregulated in human obesity. We aimed to explore the role of adipocyte-derived DPP4 in diet-induced obesity and insulin resistance with an adipose tissue-specific knockout (AT-DPP4-KO) mouse. Wild-type and AT-DPP4-KO mice were fed for 24 wk with a high fat diet (HFD) and characterized for body weight, glucose tolerance, insulin sensitivity by hyperinsulinemic-euglycemic clamp, and body composition and hepatic fat content. Image and molecular biology analysis of inflammation, as well as adipokine secretion, was performed in AT by immunohistochemistry, Western blot, real-time-PCR, and ELISA. Incretin levels were determined by Luminex kits. Under HFD, AT-DPP4-KO displayed markedly reduced circulating DPP4 concentrations, proving AT as a relevant source. Independently of glucose-stimulated incretin hormones, AT-DPP4-KO had improved glucose tolerance and hepatic insulin sensitivity. AT-DPP4-KO displayed smaller adipocytes and increased anti-inflammatory markers. IGF binding protein 3 (IGFBP3) levels were lower in AT and serum, whereas free IGF1 was increased. The absence of adipose DPP4 triggers beneficial AT remodeling with decreased production of IGFBP3 during HFD, likely contributing to the observed, improved hepatic insulin sensitivity.

Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

2009 ◽  
Vol 297 (1) ◽  
pp. E124-E133 ◽  
Author(s):  
Rodrigo P. A. Barros ◽  
Chiara Gabbi ◽  
Andrea Morani ◽  
Margaret Warner ◽  
Jan-Åke Gustafsson
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
White Adipose Tissue ◽  
Glucose Transporter ◽  
Wild Type ◽  
Glut4 Expression ◽  
Glucose Challenge ◽  
Fasting Hypoglycemia

Glucose uptake and homeostasis are regulated mainly by skeletal muscle (SM), white adipose tissue (WAT), pancreas, and the liver. Participation of estradiol in this regulation is still under intense investigation. We have demonstrated that, in SM of male mice, expression of the insulin-regulated glucose transporter (GLUT)4 is reduced by estrogen receptor (ER)β agonists. In the present study, to investigate the relative contributions of ERα and ERβ in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ER−/− mice. ERβ−/− mice were characterized by fasting hypoglycemia, increased levels of SM GLUT4, pancreatic islet hypertrophy, and a belated rise in plasma insulin in response to a glucose challenge. ERα−/− mice, on the contrary, were hyperglycemic and glucose intolerant, and expression of SM GLUT4 was markedly lower than in WT mice. Tam had no effect on glucose tolerance or insulin sensitivity in WT mice. In ERα−/− mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ERβ antagonist in SM but had no effect on WAT. In ERβ−/− mice, Tam did not affect GLUT4 in SM but acted as an ERα antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ERα and ERβ, ERβ-mediated repression of GLUT4 predominates in SM but ERα-mediated induction of GLUT4 predominates in WAT. This tissue-specific difference in dominance of one ER over the other is reflected in the ratio of the expression of the two receptors. ERα predominates in WAT and ERβ in SM.

scholarly journals Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme expression and mRNA splicing

2013 ◽  
Vol 219 (2) ◽  
pp. 173-182 ◽  
Author(s):  
P Brandimarti ◽  
J M Costa-Júnior ◽  
S M Ferreira ◽  
A O Protzek ◽  
G J Santos ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Alternative Splicing ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Insulin Clearance ◽  
Cafeteria Diet ◽  
Mrna Levels ◽  
Insulin Degrading Enzyme ◽  
Diet Induced Obesity

Insulin clearance plays a major role in glucose homeostasis and insulin sensitivity in physiological and/or pathological conditions, such as obesity-induced type 2 diabetes as well as diet-induced obesity. The aim of the present work was to evaluate cafeteria diet-induced obesity-induced changes in insulin clearance and to explain the mechanisms underlying these possible changes. Female Swiss mice were fed either a standard chow diet (CTL) or a cafeteria diet (CAF) for 8 weeks, after which we performed glucose tolerance tests, insulin tolerance tests, insulin dynamics, and insulin clearance tests. We then isolated pancreatic islets for ex vivo glucose-stimulated insulin secretion as well as liver, gastrocnemius, visceral adipose tissue, and hypothalamus for subsequent protein analysis by western blot and determination of mRNA levels by real-time RT-PCR. The cafeteria diet induced insulin resistance, glucose intolerance, and increased insulin secretion and total insulin content. More importantly, mice that were fed a cafeteria diet demonstrated reduced insulin clearance and decay rate as well as reduced insulin-degrading enzyme (IDE) protein and mRNA levels in liver and skeletal muscle compared with the control animals. Furthermore, the cafeteria diet reduced IDE expression and alternative splicing in the liver and skeletal muscle of mice. In conclusion, a cafeteria diet impairs glucose homeostasis by reducing insulin sensitivity, but it also reduces insulin clearance by reducing IDE expression and alternative splicing in mouse liver; however, whether this mechanism contributes to the glucose intolerance or helps to ameliorate it remains unclear.

scholarly journals Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats

2012 ◽  
Vol 108 (8) ◽  
pp. 1511-1518 ◽  
Author(s):  
Jéferson F. Goularte ◽  
Maria B. C. Ferreira ◽  
Gilberto L. Sanvitto
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Physical Exercise ◽  
Energy Intake ◽  
Liver Weight ◽  
Cafeteria Diet ◽  
Chow Diet ◽  
Diet Induced Obesity ◽  
Visceral Adipose

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

scholarly journals Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Christoph Hoffmann ◽  
Patrick Schneeweiss ◽  
Elko Randrianarisoa ◽  
Günter Schnauder ◽  
Lisa Kappler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Mitochondrial Respiration ◽  
Subcutaneous Adipose Tissue ◽  
Muscle Fibers ◽  
Sensitivity Index ◽  
Respiratory Capacity ◽  
Subcutaneous Adipose

Abstract Context Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. Objective To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. Design Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). Results Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (>15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. Conclusion Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

Changes in dietary sodium consumption modulate GLUT4 gene expression and early steps of insulin signaling

2004 ◽  
Vol 286 (4) ◽  
pp. R779-R785 ◽  
Author(s):  
Maristela Mitiko Okamoto ◽  
Dóris Hissako Sumida ◽  
Carla Roberta Oliveira Carvalho ◽  
Alessandra Martins Vargas ◽  
Joel Cláudio Heimann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Dietary Sodium ◽  
Glut4 Translocation ◽  
Glut4 Gene Expression

Previous studies have shown that chronic salt overload increases insulin sensitivity, while chronic salt restriction decreases it. In the present study we investigated the influence of dietary sodium on 1) GLUT4 gene expression, by Northern and Western blotting analysis; 2) in vivo GLUT4 protein translocation, by measuring the GLUT4 protein in plasma membrane and microsome, before and after insulin injection; and 3) insulin signaling, by analyzing basal and insulin-stimulated tyrosine phosphorylation of insulin receptor (IR)-β, insulin receptor substrate (IRS)-1, and IRS-2. Wistar rats were fed normal-sodium (NS-0.5%), low-sodium (LS-0.06%), or high-sodium diets (HS-3.12%) for 9 wk and were killed under pentobarbital anesthesia. Compared with NS rats, HS rats increased ( P < 0.05) the GLUT4 protein in adipose tissue and skeletal muscle, whereas GLUT4 mRNA was increased only in adipose tissue. GLUT4 expression was unchanged in LS rats compared with NS rats. The GLUT4 translocation in HS rats was higher ( P < 0.05) both in basal and insulin-stimulated conditions. On the other hand, LS rats did not increase the GLUT4 translocation after insulin stimulus. Compared with NS rats, LS rats showed reduced ( P < 0.01) basal and insulin-stimulated tyrosine phosphorylation of IRS-1 in skeletal muscle and IRS-2 in liver, whereas HS rats showed enhanced basal tyrosine phosphorylation of IRS-1 in skeletal muscle ( P < 0.05) and of IRS-2 in liver. In summary, increased insulin sensitivity in HS rats is related to increased GLUT4 gene expression, enhanced insulin signaling, and GLUT4 translocation, whereas decreased insulin sensitivity of LS rats does not involve changes in GLUT4 gene expression but is related to impaired insulin signaling.

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