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. Here, GCG is linked to type 1 diabetes mellitus.