Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis.
The nature and extent of somatostatin-induced inhibition of pancreatic endocrine secretion were studied by administration of a number of stimuli of either glucagon or insulin to over night fasted baboons with and without an infusion of linear somatostatin. The stimuli for acute-phase insulin release were intravenous pulses of glucose, tolbutamide, isoproterenol, and secretin. When given 15 min after the start of a somatostatin infusion, these agents were essentially unable to stimulate insulin secretion. Chronic insulin secretion was stimulated by infusions of either glucose or glucagon. Within 10 min of the start of a super-imposed infusion of somatostatin, insulin levels fell to less than 40 percent of prestimulus control and remained suppressed for the duration of the somatostatin infusion. Stimulation of glucagon secretion by insulin-induced hypoglycemia was also blocked by somatostatin. Plasma glucose decreased during somatostatin infusions except when superimposed upon an infusion of glucagon. Somatostatin had no effect on glucose production in a rat liver slice preparation. We conclude: (a) Somatostatin is a potent and so far universally effective inhibitor of both acute and chronic phases of stimulated insulin and glucagon secretion (b) The inhibitory effect is quickly reversible and the pattern of recovery of secretion is appropriate to prevailing signals; (c) Present evidence suggests that the effect of somatostatin on blood glucose is mediated through its effect on blood glucagon; (d) In the overnight-fasted baboon both in the basal state and 45 min into a 4-mg/kg-min glucose infusion, a somatostatin-induced fall in serum insulin levels appears to be unable to prevent a decrease in hepatic glucose production.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003864:Depression, Chemical; D005260:Female; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D000882:Haplorhini; D006706:Homeostasis / Q000187:drug effects*; D007003:Hypoglycemia / Q000139:chemically induced; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010215:Papio; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012633:Secretin / Q000494:pharmacology; D013268:Stimulation, Chemical; D014044:Tolbutamide / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D012633:Secretin; D005934:Glucagon; D014044:Tolbutamide; D005947:Glucose; D007545:Isoproterenol