Elucidation of development and improvement of leptin resistance

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Coadministration of leptin and exenatide significantly reduced food intake and body weight in obese type2 diabetic mice, compared with either monotherapy alone. Moreover, coadministration of leptin and exenatide normalized blood glucose levels accompanied by improvement of insulin sensitivity, restoration of glucose stimulated insulin secretion, normalization of triglyceride contents in non-adipose tissues, improvement of plasma glucagon levels and restoration of pancreatic insulin contents, while not each monotherapy. Pair-feeding experiments indicated that exenatide enhanced the leptin’s effects through independent mechanism of caloric restriction. These findings suggest that coadministration of leptin and exenatide could be a beneficial treatment for obese type2 diabetes by eliciting leptin’s effects.