Effect of exercise on body weight and insulin sensitivity following glucose loading in chronic leptin treated rats

ABSTRACT Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations. In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats. The results suggest that (1) cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, (2) cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and (3) in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue. J. Endocr. (1985) 106, 225–231

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Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00810.2020 ◽

2021 ◽

Author(s):

Emily J. Arentson-Lantz ◽

Jasmine Mikovic ◽

Nisha Bhattarai ◽

Christopher S. Fry ◽

Séverine Lamon ◽

...

Keyword(s):

Older Adults ◽

Skeletal Muscle ◽

Body Weight ◽

Insulin Sensitivity ◽

Bed Rest ◽

Metabolic Clearance ◽

Leucine Supplementation ◽

Respiratory Capacity ◽

Antioxidant Defense Systems ◽

Mitochondrial Respiratory

Leucine supplementation attenuates the loss of skeletal muscle mass and function in older adults during bed rest. We sought to determine if leucine could also preserve and/or restore mitochondrial function and muscle oxidative capacity during periods of disuse and rehabilitation. Healthy older adults (69.1 ± 1.1 years) consumed a structured diet with supplemental leucine (LEU: 0.06 g/ kg body weight/ meal; n=8) or alanine (CON: 0.06 g/ kg body weight/meal; n=8) during 7 days of bed rest and 5 days of inpatient rehabilitation. A 75 g oral glucose tolerance test was performed at baseline (PreBR), after bed rest (PostBR) and rehabilitation (PostRehab) and used to calculate an indicator of insulin sensitivity, metabolic clearance rate. (MCR). Tissue samples from the m. vastus lateralis were collected PreBR, PostBR, and PostRehab to assess mitochondrial respiratory capacity and protein markers of the oxidative phosphorylation and a marker of the antioxidant defense systems. During bed rest, leucine tended to preserve insulin sensitivity (Change in MCR, CON vs. LEU: -3.5 ± 0.82 vs LEU: -0.98 ± 0.88, p=0.054), but had no effect on mitochondrial respiratory capacity (Change in State 3+succinate CON vs. LEU -8.7 ± 6.1 vs. 7.3 ± 4.1 pmol O2/sec/mg tissue, p=0.10) Following rehabilitation, leucine increased ATP-linked respiration (CON vs. LEU: -8.9 ± 6.2 vs. 15.5± 4.4 pmol O2/sec/mg tissue, p=0.0042). While the expression of mitochondrial respiratory and antioxidant proteins was not impacted, leucine supplementation preserved specific pathways of mitochondrial respiration, insulin sensitivity and a marker of oxidative stress during bed rest and rehabilitation.

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Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽

10.1210/en.2015-1159 ◽

2015 ◽

Vol 156 (11) ◽

pp. 4071-4080 ◽

Cited By ~ 17

Author(s):

Amanda Hurliman ◽

Jennifer Keller Brown ◽

Nicole Maille ◽

Maurizio Mandala ◽

Peter Casson ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Insulin Sensitivity ◽

Endothelial Dysfunction ◽

Polycystic Ovary Syndrome ◽

Rat Model ◽

Polycystic Ovary ◽

Phase 1 ◽

Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

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Insulin Sensitivity and Body Weight Changes in Young White Carriers of the Codon 64 Amino Acid Polymorphism of the 3-Adrenergic Receptor Gene

Diabetes ◽

10.2337/diab.45.8.1115 ◽

1996 ◽

Vol 45 (8) ◽

pp. 1115-1120 ◽

Cited By ~ 51

Author(s):

S. A. Urhammer ◽

J. O. Clausen ◽

T. Hansen ◽

O. Pedersen

Keyword(s):

Body Weight ◽

Amino Acid ◽

Insulin Sensitivity ◽

Adrenergic Receptor ◽

Receptor Gene ◽

Weight Changes ◽

Amino Acid Polymorphism ◽

Body Weight Changes ◽

Adrenergic Receptor Gene

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Long-term activation of PKA inβ-cells provides sustained improvement to glucose control, insulin sensitivity and body weight

Islets ◽

10.1080/19382014.2016.1198457 ◽

2016 ◽

Vol 8 (5) ◽

pp. 125-134

Author(s):

Joshua A. Levine ◽

Kelly A. Kaihara ◽

Brian T. Layden ◽

Barton Wicksteed

Keyword(s):

Body Weight ◽

Insulin Sensitivity ◽

Glucose Control ◽

Sustained Improvement

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α1-Antitrypsin A treatment attenuates neutrophil elastase accumulation and enhances insulin sensitivity in adipose tissue of mice fed a high-fat diet.

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00181.2021 ◽

2021 ◽

Author(s):

Randall F. D'Souza ◽

Stewart W.C. Masson ◽

Jonathan S. T. Woodhead ◽

Samuel L James ◽

Caitlin MacRae ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Glucose Uptake ◽

Neutrophil Elastase ◽

High Fat Diet ◽

Tolerance Test ◽

Metabolic Dysfunction ◽

High Fat ◽

Insulin Tolerance

Neutrophils accumulate in insulin sensitive tissues during obesity and may play a role in impairing insulin sensitivity. The major serine protease expressed by neutrophils is neutrophil elastase (NE), which is inhibited endogenously by α1-antitrypsin A (A1AT). We investigated the effect of exogenous (A1AT) treatment on diet induced metabolic dysfunction. Male C57Bl/6j mice fed a chow or a high fat diet (HFD) were randomized to receive 3x weekly i.p injections of either Prolastin (human A1AT; 2mg) or vehicle (PBS) for 10 weeks. Prolastin treatment did not affect plasma NE concentration, body weight, glucose tolerance or insulin sensitivity in chow fed mice. In contrast, Prolastin treatment attenuated HFD induced increases in plasma and white adipose tissue (WAT) NE without affecting circulatory neutrophil levels or increases in body weight. Prolastin-treated mice fed a HFD had improved insulin sensitivity, as assessed by insulin tolerance test, and this was associated with higher insulin-dependent IRS-1 (insulin receptor substrate) and AktSer473phosphorylation, and reduced inflammation markers in WAT but not liver or muscle. In 3T3-L1 adipocytes, Prolastin reversed recombinant NE-induced impairment of insulin-stimulated glucose uptake and IRS-1 phosphorylation. Furthermore, PDGF mediated p-AktSer473 activation and glucose uptake (which is independent of IRS-1) was not affected by recombinant NE treatment. Collectively, our findings suggest that NE infiltration of WAT during metabolic overload contributes to insulin-resistance by impairing insulin-induced IRS-1 signaling.

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Adiponectin is required to mediate rimonabant-induced improvement of insulin sensitivity but not body weight loss in diet-induced obese mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90824.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. R929-R935 ◽

Cited By ~ 29

Author(s):

Stéphanie Migrenne ◽

Amélie Lacombe ◽

Anne-Laure Lefèvre ◽

Marie-Pierre Pruniaux ◽

Etienne Guillot ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Energy Homeostasis ◽

Hepatic Glucose Production ◽

Body Weight Loss ◽

Metabolic Effects ◽

Wild Type ◽

High Fat ◽

Wild Type Littermate

The increase in adiponectin levels in obese patients with untreated dyslipidemia and its mRNA expression in adipose tissue of obese animals are one of the most interesting consequences of rimonabant treatment. Thus, part of rimonabant's metabolic effects could be related to an enhancement of adiponectin secretion and its consequence on the modulation of insulin action, as well as energy homeostasis. The present study investigated the effects of rimonabant in adiponectin knockout mice (Ad−/−) exposed to diet-induced obesity conditions. Six-week-old Ad−/− male mice and their wild-type littermate controls (Ad+/+) were fed a high-fat diet for 7 mo. During the last month, animals were administered daily either with vehicle or rimonabant by mouth (10 mg/kg). High-fat feeding induced weight gain by about 130% in both wild-type and Ad−/− mice. Obesity was associated with hyperinsulinemia and insulin resistance. Treatment with rimonabant led to a significant and similar decrease in body weight in both Ad+/+ and Ad−/− mice compared with vehicle-treated animals. In addition, rimonabant significantly improved insulin sensitivity in Ad+/+ mice compared with Ad+/+ vehicle-treated mice by decreasing hepatic glucose production and increasing glucose utilization index in both visceral and subcutaneous adipose tissue. In contrast, rimonabant failed to improve insulin sensitivity in Ad−/− mice, despite the loss in body weight. Rimonabant's effect on body weight appeared independent of the adiponectin pathway, whereas adiponectin seems required to mediate rimonabant-induced improvement of insulin sensitivity in rodents.

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