Influence of somatostatin on glucagon- and epinephrine-stimulated hepatic glucose output in the dog.
Glucose kinetics were measured using [3-3H]glucose in conscious dogs during the infusion of: 1) glucagon alone; 2) glucagon plus somatostatin with insulin replacement; 3) epinephrine alone; and 4) epinephrine plus somatostatin with insulin and glucagon replacement. Infusion of glucagon alone resulted in a 10-15 mg/dl rise in plasma glucose and a transient 45% rise in glucose production. When somatostatin and insulin were added, a four- to fivefold greater rise in plasma glucose and glucose production was observed. Glucagon levels were comparable to those achieved with infusion of glucagon alone, whereas peripheral insulin levels increased three- to fourfold above baseline, suggesting adequate replacement of preinfusion portal insulin levels. Infusion of epinephrine alone produced a 40% rise in plasma glucose and a 100% rise in glucose production. When somatostatin, insulin, and glucagon were added to epinephrine, the rise in glucose production was reduced in 65% despite replacement of glucagon levels and presumably mild portal insulin deficiency. These findings suggest that somatostatin: 1) potentiates the stimulatory effect of physiologic hyperglucagonemia on glucose production independent of insulin availability and 2) blunts the stimulatory effect of physiologic increments of epinephrine independent of glucagon availability.
D000818:Animals; D001786:Blood Glucose; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005947:Glucose; D004837:Epinephrine