Temporal evolution of altered islet neurotransmitter sensitivity after VMH lesion

It has been suggested that increased insulin secretion after ventromedial hypothalamic (VMH) obesity is mediated by decreased sympathetic and increased parasympathetic neural input. The evolution of pancreatic islet adaptation was studied from 1 to 130 days after VMH lesion in rats by assessing the sensitivity of insulin secretion from incubated isolated islets to 10 mM glucose and selected acetylcholine and norepinephrine concentrations. Insulin secretion in response to glucose increased by 1 day, reaching a twofold plateau from 7 to 130 days. Sensitivity to norepinephrine increased by 1 day, whereas sensitivity to acetylcholine decreased by 2 days, and both remained altered up to 130 days. These data suggest that elevated plasma insulin concentrations characteristic of VMH obesity were associated with increased insulin secretion in response to glucose before decreased sensitivity to acetylcholine and concurrent with increased sensitivity to norepinephrine. We conclude that these compensatory responses, which shift the islet to a new operating point secondary to altered neural input, are essential to pancreatic adaptation in VMH obesity.