|dc.description.abstract||Central leptin increases peripheral insulin sensitivity through unknown mechanisms. Central insulin signaling may also contribute to peripheral insulin sensitivity. To clarify the relationships among central leptin, central insulin, peripheral insulin sensitivity, and adiponectin, we examined the effects of intracerebroventricular leptin and insulin on peripheral insulin sensitivity and adiponectin concentrations in streptozotocin (STZ)-induced diabetic rats. Rats were cannulated in the lateral ventricle. Intravenous STZ was injected to induce diabetes. After establishment of hyperglycemia in STZ-treated rats, insulin (10 mU/day), leptin (10 µg/day), or vehicle was administered daily for 10 days. After one week of central administration, in vivo insulin sensitivity was measured by injecting IV insulin (0.025 U/kg body weight) and measuring blood glucose concentration 15 minutes after the injection. Rats treated with central leptin had increased peripheral insulin sensitivity. In addition, blood glucose concentrations in diabetic rats were normalized by the 4th day of receiving central leptin administration. Central insulin administration did not affect insulin sensitivity or normalize blood glucose concentrations. Compared to control diabetic rats, diabetic rats receiving central leptin administration, but not diabetic rats receiving central insulin administration, had higher circulating adiponectin concentrations and lower serum and muscle triglyceride concentrations. Therefore, central leptin, but not central insulin, enhances peripheral insulin sensitivity. Adiponectin may be a down-stream target for central leptin signaling.
In the second study, we examined the hypothesis that the sympathetic nervous system is involved in mediating the ability of central leptin to normalize blood glucose concentrations in diabetic rats. A group of rats were chemically sympathectomized with guanethidine (100 mg/kg body weight). Rats were cannulated in the lateral ventricle and then made diabetic with STZ treatment. After establishment of diabetes, rats were given daily injections of leptin (10 ?g/day) or vehicle. Leptin decreased blood glucose concentrations equally in both guanethidine-treated and vehicle-treated diabetic rats. This appears to suggest that an intact sympathetic nervous system is not required for central leptin to enhance peripheral insulin sensitivity. However, sympathetic activity was not completely blocked in some tissues (spleen and brown adipose tissue) and not blocked at all in other tissues (liver and white adipose tissue). Therefore, further study is needed to determine the role of the sympathetic nervous system in mediating central leptin’s effect on peripheral insulin sensitivity in diabetic rat.||en_US