Effect of glucagon on glucose production during insulin deficiency in the dog.
The aim of the present experiments was to determine the effects of basal glucagon on glucose production after induction of prolonged insulin lack in normal conscious dogs fasted overnight. A selective deficiency of insulin or a combined deficiency of both pancreatic hormones was created by infusing somatostatin alone or in combination with an intraportal replacement infusion of glucagon. Glucose production (GP) was measured by a primed constant infusion of [3H-3]glucose, and gluconeogenesis (GNG) was assessed by determining the conversion rate of circulating [14C]alanine and [14C]lactate into [14C]glucose. When insulin deficiency was induced in the presence of basal glucagon the latter hormone caused GP to double and then to decline so that after 4 h it had returned to the conrol rate. The conversion of alanine and lactate into glucose, on the other hand, increased throughout the period of insulin lack. Withdrawal of glucagon after GP had normalized resulted in a 40% fall in GP, a 37% decrease in GNG, and a marked decrease in the plasma glucose concentration. Induction of insulin deficiency in the absence of basal glucagon resulted in an initial (30%) drop in GP followed by a restoration of normal GP after 2--3 h and moderately enhanced glucose formation from alanine and lactate. It can be concluded that (a) the effect of relative hyperglucagonemia on GP is short-lived; (b) the waning of the effect of glucagon is attributable solely to a diminution of glycogenolysis because GNG remains stimulated; (c) basal glucagon markedly enhances the GNG stimulation apparent after induction of insulin deficiency; and (d) basal glucagon worsens the hyperglycemia pursuant on the induction of insulin deficiency both by triggering an initial overproduction of glucose and by maintaining the basal production rate thereafter.
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004285:Dogs; D005260:Female; D005934:Glucagon / Q000097:blood / Q000172:deficiency / Q000494:pharmacology*; D005943:Gluconeogenesis; D006943:Hyperglycemia / Q000209:etiology; D007328:Insulin / Q000172:deficiency* / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008297:Male; D013004:Somatostatin / Q000494:pharmacology; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D013004:Somatostatin; D005934:Glucagon; D000409:Alanine