Given that both hyperglycemia and recurrent hypoglycemia/glucoprivation suppress hypothalamic AMPK activation (6, 13) and that direct genetic suppression of VMH AMPK expression/activity suppresses the glucagon and adrenaline responses to hypoglycemia (12), it is plausible that hypothalamic AMPK activity is blunted in diabetes, leading, at least in part, to defective CRR. This evidence concerns the gene GCG and diabetes mellitus.