LOCAL VENTROMEDIAL HYPOTHALAMUS GLUCOSE PERFUSION BLOCKS COUNTERREGULATION DURING SYSTEMIC HYPOGLYCEMIA IN AWAKE RATS

The ventromedial hypothalamic nucleus (VMH) is necessary for the integ rated hormonal response to hypoglycemia. To determine the role of the VMH as a glucose sensor, we performed experiments designed to specific ally prevent glucopenia in the VMH, while producing hypoglycemia elsew here. We used awake chronically catheterized rats, in which local VMH glucose perfusion (100 mM or 15 mM of D-glucose) was combined with a s equential euglycemichypoglycemic clamp. In two control groups the VMH was perfused either with (a) an iso-osmotic solution lacking glucose, or with (b) nonmetabolizable L-glucose (100 mM). During systemic hypog lycemia glucagon and catecholamine concentrations promptly increased i n the control animals perfused with either 100 mM L-glucose or the iso -osmotic solution lacking glucose. In contrast, glucagon, epinephrine and norepinephrine release was inhibited in the animals in which the V MH was perfused with D-glucose; hormonal secretion was partially suppr essed by the VMH perfusion with 15 mM D-glucose and suppressed by simi lar to 85% when the VMH was perfused with 100 mM D-glucose, as compare d with the control groups. We conclude that the VMH must sense hypogly cemia for full activation of catecholamine and glucagon secretion and that it is a key glucose sensor for hypoglycemic counterregulation.