Notably, central leptin administration improves insulin-deficient diabetes in rodents independent of leptin-induced reduction in body weight and food intake [42, 43], improves glucose homeostasis in obese mice independent of leptin-induced changes in body weight [44], and has acute effects on hepatic and peripheral glucose flux [45–48]. This evidence concerns the gene INS and hyperinsulinemic hypoglycemia, familial, 4.