Feeding and neuroendocrine responses after recurrent insulin-induced hypoglycemia

Prior exposure to hypoglycemia impairs neuroendocrine counterregulatory responses (CRR) during subsequent hypoglycemia. Defective CRR to hypoglycemia is a component of the clinical syndrome hypoglycemia-associated autonomic failure (HAAF). Hypoglycemia also potently stimulates food intake, an important behavioral CRR. Because the increased feeding response to hypoglycemia is behavioral and not hormonal, we hypothesized that it may be regulated differently with recurrent bouts of hypoglycemia. To test this hypothesis, we simultaneously evaluated neuroendocrine CRR and food intake in rats experiencing one or three episodes of insulin-induced hypoglycemia. As expected, recurrent hypoglycemia significantly reduced neuroendocrine hypoglycemic CRR. Epinephrine (E), norepinephrine (NE) and glucagon responses 120 min after insulin injection were significantly reduced in recurrent hypoglycemic rats, relative to rats experiencing hypoglycemia for the first time. Despite these neuroendocrine impairments, food intake was significantly elevated above baseline saline intake whether rats were experiencing a first (hypoglycemia: 3.4+/-0.4 g vs. saline: 0.94+/-0.3 g, P<0.05) or third hypoglycemic episode (hypoglycemia: 3.8+/-0.3 g vs. saline: 1.2+/-0.3 g, P<0.05). These findings demonstrate that food intake elicited in response to hypoglycemia is not impaired as a result of recurrent hypoglycemia. Thus, neuroendocrine and behavioral (stimulation of food intake) CRR are differentially regulated by recurrent hypoglycemia experience.