PRKAA2 and Hyperglycemia: 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.