Central leptin gene therapy ameliorates diabetes type 1 and 2 through two independent hypothalamic relays; a benefit beyond weight and appetite regulation

摘要: Although its role in energy homeostasis is firmly established, the evidence accumulated over a decade linking adipocyte leptin-hypothalamus axis pathogenesis of diabetes mellitus has received little attention contemporary thinking. In this context various lines are collated here to show that (1) under direction leptin two independent relays emanating from hypothalamus restrain insulin secretion pancreas and mobilize peripheral organs--liver, skeletal muscle brown adipose tissue--to upregulate glucose disposal, (2), insufficiency produced by either leptinopenia or restriction transport across blood brain barrier due hyperleptinemia obesity aging, initiate antecedent pathophysiological sequalae type 1 2. Further, we document efficacy replenishment vivo, especially supplying it with aid gene therapy, preventing sequalae--hyperinsulinemia, resistance hyperglycemia--in animal models clinical paradigms 2 without attendant obesity. Overall, new insights on long-lasting antidiabetic potential hypothalamic engendered central therapy preclinical safety indicators rodents warrant further validation subhuman primates humans.