scholarly journals Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats

2007 ◽  
Vol 99 (4) ◽  
pp. 806-812 ◽  
Author(s):  
M. G. Sridhar ◽  
R. Vinayagamoorthi ◽  
V. Arul Suyambunathan ◽  
Z. Bobby ◽  
N. Selvaraj
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Insulin Signalling ◽  
Bitter Gourd ◽  
High Fat ◽  
Fat Feeding

The aim of this present study was to investigate the effect of bitter gourd extract on insulin sensitivity and proximal insulin signalling pathways in high-fat-fed rats. High-fat feeding of male Wistar rats for 10 weeks decreased the glucose tolerance and insulin sensitivity compared to chow-fed control rats. Bitter gourd extract supplementation for 2 weeks (9th and 10th) of high-fat feeding improved the glucose tolerance and insulin sensitivity. In addition bitter gourd extract reduced the fasting insulin (43 (se 4·4) v. 23 (se 5·2) μU/ml, P < 0·05), TAG (134 (se 12) v. 96 (se 5·5) mg/dl, P < 0·05), cholesterol (97 (se 6·3) v. 72 (se 5·2) mg/dl, P < 0·05) and epidydimal fat (4·8 (se 0·29) v. 3·6 (se 0·24) g, P < 0·05), which were increased by high-fat diet (HFD). High-fat feeding and bitter gourd supplementation did not have any effect on skeletal muscle insulin receptor, insulin receptor subtrate-1 (IRS-1) and insulin- stimulated insulin receptor tyrosine phosphorylation compared to chow-fed control rats. However high-fat feeding for 10 weeks reduced the insulin-stimulated IRS-1 tyrosine phosphorylation compared to control rats. Bitter gourd supplementation together with HFD for 2 weeks improved the insulin-stimulated IRS-1 tyrosine phosphorylation compared to rats fed with HFD alone. Our results show that bitter gourd extract improves insulin sensitivity, glucose tolerance and insulin signalling in HFD-induced insulin resistance. Identification of potential mechanism(s) by which bitter gourd improves insulin sensitivity and insulin signalling in high-fat-fed rats may open new therapeutic targets for the treatment of obesity/dyslipidemia-induced insulin resistance.

Insulin signalling, exercise and cellular integrity

2003 ◽  
Vol 31 (6) ◽  
pp. 1281-1285 ◽  
Author(s):  
J.P. Kirwan ◽  
L.F. del Aguila
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Eccentric Exercise ◽  
Insulin Signalling ◽  
Serine Phosphorylation ◽  
Marathon Running ◽  
Glut 4 ◽  
Tnf Α

Although the effects of exercise on insulin sensitivity are generally positive, eccentric exercise presents a paradox because it induces a transient state of insulin resistance that persists for up to 48 h after the exercise bout. Excessive eccentric contractions, such as prolonged downhill running, or marathon running, causes muscle damage and disruption of the integrity of the cell. Down-regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)-associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation and activity and glucose transporter (GLUT-4) protein content, are evident in skeletal muscle after eccentric exercise. Furthermore, increased tumour necrosis factor α (TNF-α) secretion from monocytes is associated with the decrease in PI3K activity after this type of exercise. Recent studies have shown that TNF-α can increase IRS-1 serine/threonine phosphorylation, which impairs IRS-1 docking to the insulin receptor, and this inhibits insulin signalling. Thus a unifying hypothesis to explain insulin resistance after eccentric exercise may include inflammation arising from the disruption of muscle-cell integrity, leading to an acute-phase response that includes TNF-α, with the latter inhibiting insulin signalling and subsequent metabolic events. In contrast, exercise training increases insulin signalling and GLUT-4 expression, decreases TNF-α expression in skeletal muscle, and is associated with enhanced insulin sensitivity. These observations highlight the complexity of the cellular and molecular adaptations to exercise. Understanding these adaptations is essential in order to establish a sound theoretical basis for recommending exercise as a therapeutic intervention for insulin resistance and type 2 diabetes.

Reduced β-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding

1999 ◽  
Vol 277 (4) ◽  
pp. E659-E667 ◽  
Author(s):  
Karl J. Kaiyala ◽  
Ronald L. Prigeon ◽  
Steven E. Kahn ◽  
Stephen C. Woods ◽  
Daniel Porte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Chow Diet ◽  
High Fat ◽  
Β Cell ◽  
Intravenous Glucose ◽  
Β Cell Function ◽  
Fat Feeding

The ability to increase β-cell function in the face of reduced insulin sensitivity is essential for normal glucose tolerance. Because high-fat feeding reduces both insulin sensitivity and glucose tolerance, we hypothesized that it also reduces β-cell compensation. To test this hypothesis, we used intravenous glucose tolerance testing with minimal model analysis to measure glucose tolerance ( K g), insulin sensitivity (SI), and the acute insulin response to glucose (AIRg) in nine dogs fed a chow diet and again after 7 wk of high-fat feeding. Additionally, we measured the effect of consuming each diet on 24-h profiles of insulin and glucose. After high-fat feeding, SI decreased by 57% ( P = 0.003) but AIRg was unchanged. This absence of β-cell compensation to insulin resistance contributed to a 41% reduction of K g( P = 0.003) and abolished the normal hyperbolic relationship between AIRg and SI observed at baseline. High-fat feeding also elicited a 44% lower 24-h insulin level ( P = 0.004) in association with an 8% reduction of glucose ( P = 0.0003). We conclude that high-fat feeding causes insulin resistance that is not compensated for by increased insulin secretion and that this contributes to the development of glucose intolerance. These effects of high-fat feeding may be especially deleterious to individuals predisposed to type 2 diabetes mellitus.

Reduced insulin receptor signaling in the obese spontaneously hypertensive Koletsky rat

1997 ◽  
Vol 273 (5) ◽  
pp. E1014-E1023 ◽  
Author(s):  
Jacob E. Friedman ◽  
Tatsuya Ishizuka ◽  
Sha Liu ◽  
Craig J. Farrell ◽  
David Bedol ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Glucose Intolerance ◽  
Leptin Receptor ◽  
Spontaneously Hypertensive Rat ◽  
Regulatory Subunit ◽  
Oral Glucose ◽  
Spontaneously Hypertensive

Insulin resistance is associated with both obesity and hypertension. However, the cellular mechanisms of insulin resistance in genetic models of obese-hypertension have not been identified. The objective of the present study was to investigate the effects of genetic obesity on a background of inherited hypertension on initial components of the insulin signal transduction pathway and glucose transport in skeletal muscle and liver. Oral glucose tolerance testing in SHROB demonstrated a sustained postchallenge elevation in plasma glucose at 180 and 240 min compared with lean spontaneously hypertensive rat (SHR) littermates, which is suggestive of glucose intolerance. Fasting plasma insulin levels were elevated 18-fold in SHROB. The rate of insulin-stimulated 3- O-methylglucose transport was reduced 68% in isolated epitrochlearis muscles from the SHROB compared with SHR. Insulin-stimulated tyrosine phosphorylation of the insulin receptor β-subunit and insulin receptor substrate-1 (IRS-1) in intact skeletal muscle of SHROB was reduced by 36 and 23%, respectively, compared with SHR, due primarily to 32 and 60% decreases in insulin receptor and IRS-1 protein expression, respectively. The amounts of p85α regulatory subunit of phosphatidylinositol-3-kinase and GLUT-4 protein were reduced by 28 and 25% in SHROB muscle compared with SHR. In the liver of SHROB, the effect of insulin on tyrosine phosphorylation of IRS-1 was not changed, but insulin receptor phosphorylation was decreased by 41%, compared with SHR, due to a 30% reduction in insulin receptor levels. Our observations suggest that the leptin receptor mutation fak imposed on a hypertensive background results in extreme hyperinsulinemia, glucose intolerance, and decreased expression of postreceptor insulin signaling proteins in skeletal muscle. Despite these changes, hypertension is not exacerbated in SHROB compared with SHR, suggesting these metabolic abnormalities may not contribute to hypertension in this model of Syndrome X.

scholarly journals Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice

2019 ◽  
Vol 317 (6) ◽  
pp. C1172-C1182 ◽  
Author(s):  
Min-Gyeong Shin ◽  
Hye-Na Cha ◽  
Soyoung Park ◽  
Yong-Woon Kim ◽  
Jong-Yeon Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Control Diet ◽  
In Vivo Studies ◽  
Selenoprotein W ◽  
Obese Mice ◽  
High Fat

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

2006 ◽  
Vol 100 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
Jong Sam Lee ◽  
Srijan K. Pinnamaneni ◽  
Su Ju Eo ◽  
In Ho Cho ◽  
Jae Hwan Pyo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

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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