Changes in glucagon do not play an essential role in the glucoregulatory responses to mild hyperinsulinemia in dogs.
To examine whether an increase in the glucagon concentration is essential for restoring hepatic glucose output following moderate decrements in blood glucose, we used isotope dilution techniques in trained conscious dogs (n = 5) to measure glucose production (Ra) and glucose utilization (Rd) during mild hyperinsulinemia (19 +/- 1 mU/l). In Study A, when insulin was infused to raise plasma insulin (IRI) from 13 +/- 2 to 19 +/- 1 mU/l, basal glucose (93 +/- 3 mg/dl) fell at a rate of 0.37 +/- 0.06 mg/dl/min over 30 min. Ra fell from 2.8 +/- 0.4 mg/kg/min by 0.5 +/- 0.1 mg/kg/min at 20 min (P less than 0.05), but recovered to baseline by 30 min; glucagon (IRG) fell transiently but returned to baseline by 45 min. In Study B, endogenous secretion of IRI and IRG was suppressed by infusion of somatostatin (0.2 microgram/kg/min), while peripheral concentrations were maintained constant by replacing glucagon (0.65 ng/kg/min) and insulin (0.225 mU/kg/min). Steady-state baseline plasma IRI, IRG, glucose and glucose turnover rates were similar to Study A; hyperinsulinemia was then induced as in Study A. Glucose fell by 0.78 +/- 0.19 mg/dl/min over 30 min and, as in Study A, Ra decreased transiently, but recovered to baseline by 30 min. The restoration of Ra occurred in study B despite constant IRG, and preceded later increments in cortisol and catecholamines at 60-90 min. Thus, in both studies A and B, Ra recovered to baseline without an increase in IRG and before the onset of significant hypoglycemia (glucose 83 +/- 1 and 70 +/- 1 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000378:metabolism / Q000502:physiology*; D006946:Hyperinsulinism / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon