Hyperglycemia and beta-cell adaptation during prolonged somatostatin infusion with glucagon replacement in man.
To assess the relationship between beta-cell function and the level and duration of hyperglycemia during generalized beta-cell impairment, we studied the effects of acute and prolonged infusion of somatostatin in seven normal men. Twenty minutes after beginning an acute infusion of somatostatin (200 microgram/h) plus glucagon replacement (0.75 ng/kg/min), plasma glucose (PG) remained unchanged, but plasma insulin (IRI) and acute insulin response to isoproterenol had fallen markedly. Seventy minutes after beginning somatostatin-plus-glucagon, a rise in PG was associated with an increase in the acute insulin response to isoproterenol, though not to the control level. In a separate study, after 46 h of the somatostatin-plus-glucagon infusion, at a glucose level similar to the 70-min level, plasma insulin had returned nearly to the control level and the acute insulin response to isoproterenol had returned completely to the control level. Such increases inb basal and stimulated insulin secretion most likely represent a time-dependent adaptation by the beta-cells to the persistent hyperglycemia. First- and second-phase insulin responses to intravenous glucose were markedly inhibited after 46 h of somatostatin-plus-glucagon. In summary, a 46-h infusion of somatostatin with glucagon replacement in humans leads to hyperglycemia, a slightly diminished basal insulin level, markedly decreased insulin responses to glucose, and an insulin response to isoproterenol maintained at a normal level by acute and probably chronic adaptation to the hyperglycemia. We speculate that beta-cell adaptation to hyperglycemia may explain the similar abnormalities of islet function observed in patients with NIDDM.
D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D013004:Somatostatin / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose; D007545:Isoproterenol