Oral glucose augments the counterregulatory hormone response during insulin-induced hypoglycemia in humans

It has been suggested that the counterregulatory hormone (CRH) response to acute hypoglycemia is triggered via glucose sensors situated in either the hypothalamus or the portohepatic area. If the latter were critical during h ypoglycemia, one would anticipate that ingestion of glucose, by raising glu cose levels in the portal circulation, should attenuate CRH responses previ ously described in animal studies. To evaluate the effect of raising portal , but not peripheral, glucose levels during insulin-induced hypoglycemia, w e performed hypoglycemic clamp studies in five healthy adult males on two o ccasions. On one occasion, subjects received oral glucose (OG) (25 g) durin g hypoglycemia; and on one occasion, noncarbohydrate-containing drink of eq ual volume, while maintaining plasma glucose at 55 +/- 2 mg/dL (3.08 mmol/L ). As a result, there were no significant differences in systemic plasma gluco se levels between the two hypoglycemic clamp studies, and basal CRH concent rations were also similar. As expected, there was a brisk rise in all CRH d uring the control (hypoglycemia+noncarbohydrate drink) study. In the experi mental study, administration of OG (hypoglycemia+OG), to raise intraportal glucose levels during systemic hypoglycemia, did not attenuate CRH response s. Indeed, OG enhanced the rise in epinephrine, glucagon, and GH. Increases in cortisol and norepinephrine did not differ between the two stu dies. Therefore, our data suggest that increasing the level of glucose in the por tal vein above that in the systemic circulation, during hypoglycemia, enhan ces (rather than suppresses) CRH responses. Thus, ingestion of glucose may reverse hypoglycemia directly by provision of substrate, as well as indirec tly by stimulating counteregulatory mechanisms.