Chronic hypoglycemia and diabetes impair counterregulation induced by localized 2-deoxy-glucose perfusion of the ventromedial hypothalamus in rats

Previous studies have demonstrated that the ventromedial hypothalamus (VMH) plays a critical role in sensing and responding to systemic hypoglycemia. To evaluate the mechanisms of defective counterregulation caused by iatroge nic hypoglycemia and diabetes per se, we delivered 2-deoxy-glucose (2-DG) v ia microdialysis into the VMH to produce localized cellular glucopenia in t he absence of systemic hypoglycemia. Three groups of awake chronically cath eterized rats were studied: 2) nondiabetic (with a mean daily glucose [MDG] of 6.9 mmol/l) BE control rats (n = 5); 2) chronically hypoglycemic nondia betic (3-4, weeks, with an MDG of 2.7 mmol/l) BE rats (n = 5); and 5) moder ately hyperglycemic insulin-treated diabetic (with an MDG of 12.4 mmol/l) B E rats (n = 8). In hypoglycemic rats, both glucagon and catecholamine respo nses to VMH glucopenia were markedly (77-93%) suppressed. In diabetic rats, VMH 2-DG perfusion was totally ineffective in stimulating glucagon release . The epinephrine response, but not the norepinephrine response, was also d iminished by 38%, in the diabetic group. We conclude that impaired counterr egulation after chronic hypoglycemia may result from alterations of the VMH or its efferent pathways. In diabetes, the capacity of VMH glucopenia to a ctivate the sympathoadrenal system is only modestly diminished; however the communication between the VMH and the alpha-cell is totally interrupted.