Search for the hypoglycemia receptor using the local irrigation approach

Abstract

To elucidate the loci for the putative glucoreceptors responding to hypoglycemia we introduced 'brain' and 'liver' clamps. Systemic hypoglycemia was induced by insulin infusion while the area of interest (ie. forebrain, hindbrain, portal-hepatic region) was maintained euglycemic via local glucose irrigation. Utilizing this approach, there appear to be no glucoreceptors residing exclusively in either the forebrain or hindbrain which are essential for the sympathoadrenal response to hypoglycemia. This is true for both moderate and severe hypoglycemic conditions. The possibility of a redundant glucoreceptor system within the brain, as suggested by a subsequent study, remains to be confirmed. The portal-hepatic glucoreceptors appear essential to engendering the full counterregulatory response. Establishing euglycemia across the portal-hepatic region inhibits the sympathoadrenal response to moderate hypoglycemia by over 40%. Further, despite prevailing hypoglycemia and significant elevations in counter-regulatory hormones, the liver demonstrated net glucose extraction during the liver clamp, suggestive of overriding neural input to the liver. Thus, the hepatic afferents appear to be very important for the counterregulatory response to hypoglycemia.