Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis.

Abstract

A B S T R A C T The nature and extent of somatostatininduced inhibition of pancreatic endocrine secretion were studied by administration of a number of stimuli of either glucagon or insulin to overnight 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 superimposed infusion of somatostatin, insulin levels fell to less than 40% 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 somatostatininduced fall in serum insulin levels appears to be unable to prevent a decrease in hepatic glucose production.

The effect of somatostatin on pancreatic endocrine responses mediated via the parasympathetic innervation in the conscious calf.

“…In addition to blocking the release of insulin mediated via the parasympathetic innervation somatostatin is known to suppress the direct insulinotropic action of glucose (Sakurai, Dobbs & Unger, 1974;Chideckel, Palmer, Koerker, Ensinck, Davidson & Goodner, 1975; Leblanc, Anderson, Sigel & Yen, 1975). This was reflected in the present experiments by the rapid rise in plasma insulin concentration without a proportional increase in plasma glucagon concentration, that occurred in response to hyperglycaemia following administration of 2-deoxyglucose, when the infusions of somatostatin were discontinued (Fig.…”

Alpha cell function in health and disease: influence of glucagon-like peptide-1

“…Although other non-glucose secretagogues, such as isoproterenol, are also used in provocative tests of beta cell function [26], bolus administration of isoproterenol is less effective than arginine in stimulation of acute glucagon release in humans [27]. Acute insulin-induced hypoglycaemia has also been used to assess alpha cell [9] NEFA [8] Parasympathetic nerves [10] Ketones [7] Adrenaline (epinephrine) [112] Insulin [113] Oxytocin [114] Somatostatin [115] Vasopressin [116] Secretin [117] GIP [118] GLP-1 [54] PACAP [119] Carbohydrate meal [18] GRP [120] CCK [121] VIP [122] Protein meal [18] Stress [20] Hypoglycaemia [3] GRP gastrin-releasing peptide; PACAP pituitary adenylate cyclaseactivating polypeptide; VIP vasoactive intestinal polypeptide function in humans [28], although arginine stimulation tests clearly pose less risk and are more routinely employed.…”

Somatostatin — both hormone and neurotransmitter?

“…While investigating the effect of somatostatin on GH release, several groups made the unexpected observation that the peptide also inhibited insulin release [1,57,35,39,69,18,32,33,62,29,34]. This was particularly interesting in view of the hypothesis that impaired insulin release is a primary derangement in diabetes mellitus.…”