Decreased Insulin Binding, Glucose Transport, and Glucose Metabolism in Soleus Muscle of Rats Fed a High Fat Diet

Abstract

The relationship between diet and insulin sensitivity was examined in isolated soleus muscle from 10-wk-old lean Zucker rats. Rats were fed either a high fat or high carbohydrate diet that had 67% of calories as fat or carbohydrate, respectively, for 10 days. Plasma insulin but not plasma glucose concentrations were significantly elevated in high-fat-fed rats, indicating that a state of insulin resistance existed. The mechanisms responsible for the insulin resistance were studied by measuring insulin binding, 2-deoxyglucose uptake, and glucose metabolism in soleus muscle. The soleus muscle from the high-fat-fed rats bound significantly less insulin than high carbohydrate control rats under equilibrium binding conditions. The 35% decrease in insulin binding at maximal insulin concentrations resulted from a decrease in insulin receptor number but no change in receptor affinity. Maximal insulin-stimulated 2-deoxyglucose uptake was reduced in soleus muscle from high-fat-fed rats when compared with high carbohydrate controls. A decrease in postmembrane basal and insulin-stimulated glucose utilization was produced by high rat feeding and varied depending upon the pathway involved. An estimate of glycolysis (3H2O) formation from [5-3H]glucose) and glucose oxidation (14CO2 production from 14C-glucose) demonstrated a greater decrease in basal and insulin-stimulated utilization than in [5-3H]glucose conversion to [3H]glycogen. These results suggest that multiple sites are responsible for the observed insulin resistance in soleus muscle after high fat feeding.

Anti–diabetic activity of the semi–purified fractions of Averrhoa bilimbi in high fat diet fed–streptozotocin–induced diabetic rats

“…Similar observation was obtained in STZ-diabetic rats that the hepatic glycogen content tended to be higher in the AF-and metformin treated group (Pushparaj et al, 2001). It has been documented that consumption of high fat or high simple sugar diets can lead to insulin resistance in rats (Grundlege and Thenen, 1982;Storlien et al, 1991;Storlien et al, 1993). The high fat feeding induced insulin resistance initially in rat liver and adipose tissues, followed by impaired glucose metabolism skeletal tissues.…”

Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats

“…High-fructose feeding leads to peripheral insulin resistance (Susini and Lavau, 1978;Grundleger and Thenen, 1982;Vrana and Kazdova, 1983). Animals fed a diet high in fructose produce a model of hyperlipidaemia, insulin resistance, and hyperinsulinemia with accompanying mild hypertension (Reaven et al, 1990;Brands and Hall, 1992;Martinez et al, 1994;Patrick et al, 1998).…”

Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities

“…Rodent models of genetic or acquired obesity-related cardiac dysfunction have utility for understanding cardiomyopathies in the setting of INS resistance or diabetes. It is well established that animals fed high-fat diets consistently develop INS resistance, impaired glucose tolerance, decreased energy expenditure, and obesity (35,49,93). Despite differences in heart rate, as well as contractile and ion channel protein isoforms, rodent models manifest similar cardiomyopathies as humans in conditions such as obesity, INS resistance, and diabetes.…”