J Korean Diabetes Assoc.
1998 Jun;22(2):231-242.
Effect of Exercise Training on Insulin Sensitivity and Intracellular Glucose Metabolism in Skeletal Muscle
of High Fat-fed Rats
Abstract
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BACKGROUND: Insulin resistance is a major characteristic of non-insulin-dependent diabetes mellitus and obesity.
Many studies have indicated that increased intake of fat are associated with obesity and insulin resistance. On the
other hand, chronic exercise is known to improve insulin sensitivity. However, the mechanisms by which high fat diet
induces insulin resistance and exercise trainmg improves insulin sensitivity are not established. This study was
undertaken to examine the mechanisms by which high fat diet and exercise training affect the insulin sensitivity in
the whole body and in skeletal muscles. METHODS: Male Sprague-Dawley rats were divided into three groups: high
fat sedentary group, high fat exercise group, and control(low fat sedentary) group. High fat diet consists of 66.5%
fat and 12.5% carbohydrate, and control(low fat) diet consists of 12 5% fat and 66.5% carbohydrate. Exercise training
was performed by swimming three hours per day. After 3 weeks, animals underwent hyperinsulinemic euglycemic
clamp study to measure whole body glucose metabolic fluxes. Glycogen synthase activity and glucose-6-phosphate
(G-6-P) levels were measured in skeletal muscle at the end of the clamp study. RESULTS: In the high fat diet group,
whole body glycolysis and glycogen synthesis were decreased. Exercise training reversed the insulin resistance
induced by high fat diet by increasing both glycolysis and glycogen synthesis. Glycogen synthase activity in skeletal
muscle was reduced in high fat diet group, and it was partially reversed by exercise training. G-6-P level in skeletal
muscle was increased in high fat diet group, and it was further increased by exercise training. CONCLUSION: These
results
suggested that the insulin resistance in high fat diet-fed rats is due to the impairment in glucose metabolism
at sites distal to G-6-P, i.e. glycolysis and glycogen synthesis. In contrast, the improvement in insulin sensitivity by
exercise training in high fat-fed rats is primarily due to the increased glucose metabolic flux proximal to G-6-P, i.e.
glucose transport and phosphorylation.