| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 90 === Leptin, a 16 kD product of the ob gene is predominantly produced in adipose tissue and secreted into the circulation. Leptin acts as a hormonal factor that signals the size of fat depots to the hypothalamic centers and regulates food intake and energy expenditure. Except in the leptin—deficient ob/ob mouse, mRNA levels and serum protein levels are increased in all models of rodent obesity. Similar regulatory phenomena have been observed in overweight people, hypertensive and type II diabetic patients. The functional leptin receptor OB-Rb has been reported to express in many peripheral tissues including fat pads, pancreatic islets and endothelium cells indicated as target locations for leptin action. Recent findings on leptin affecting glucose utilization suggest that leptin might also modulate insulin secretion and action. Many metabolic disorders such as obesity and diabetes are related with malfunctions of glucose metabolism and strongly associated with insulin resistance. However, the involvements of leptin in the pathophysiology of insulin resistance were not clear. The purposes of this study were (1) to examine the acute effect of leptin on insulin-stimulated glucose uptake in adipocytes isolated from normal rats; (2) to measure the plasma concentration of leptin to observe whether hyperleptinemia can be induced on insulin resistant rats caused by fructose diet; (3) to study the mRNA expression of leptin on various fat depots in fructose-fed rats. Twenty male Sprague-Dawley rats initially weighing 250-300 g were divided into two groups, one group fed with standard Purina Chow as control and the other group fed with 60% of fructose diet. The dietary manipulation lasted for 12 weeks. The systolic blood pressure was monitored by tail-cuff method. Plasma levels of insulin and leptin were measured by radioimmunoassay. Plasma glucose concentration was determined by glucose analyzer. In normal rats, leptin impaired the insulin-stimulated glucose uptake in adipocytes. During fructose feeding, non-fasting plasma leptin concentrations were significantly higher in fructose-fed rats than control rats on 1st week. Fructose-fed rats caused a significant increase in non-fasting plasma insulin levels on 2nd week. Thereafter, blood pressure increased after 7th week. Non-fasting plasma glucose and body weight were significantly higher in fructose-fed rats than control rats on 8th week. Insulin resistance was observed on the7th week by oral glucose tolerance test in vivo. These results indicated that fructose diet could cause a sequential of metabolic abnormalities, including hyperleptinemia, hyperinsulinemia, insulin resistance and hypertension. In fructose-fed rats, leptin mRNA expression is higher than control rats. Regression analysis showed that leptin levels were associated with blood pressure and insulin levels. Our data suggest that leptin may impair insulin-stimulated glucose uptake in adipocytes. In addition, hyperleptinemia in fructose-fed rats may be related to the pathophysiology of insulin resistance.
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