Although a decrease in glucagon level does not always induce amelioration of hyperglycemia (1, 16, 29, 34) and although glucose-lowering effects have been reported to precede a decrease in glucagon levels in models of type I diabetes with total insulin deficiency (38), reduction of glucagon levels is the candidate best associated with the mediation of the leptin effects in our models. The gene discussed is GCG; the disease is Hyperglycemia.