Somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone, inhibits basal insulin secretion in fasted cats and rats. In fasted baboons both basal and arginine-stimulated secretion of insulin and glucagon are inhibited. Somatostatin appears to act directly on the endocrine pancreas. The action is dose-related, rapid in onset, and readily reversed.

In overnight fasted rhesus monkeys, synchronous, regular oscillations occurred in the plasma concentrations of glucose, insulin, and glucagon. The oscillations displayed a period averaging 9 minutes. The amplitudes for insulin and glucagon were ten and five times greater than for glucose. Insulin cycled in and glucagon out of phase with glucose. In baboons, oscillations of glucose and insulin were smaller than in rhesus monkeys, while in man, regular oscillations were not observed.

In vivo beta-cell function tests are used increasingly in humans during the preclinical phase of insulin-dependent diabetes mellitus (IDDM), but the severity of the beta-cell loss responsible for the abnormalities seen in these tests is unknown. We have measured several physiological beta-cell function tests--fasting plasma glucose, glucose disappearance constant, fasting insulin, acute insulin responses to arginine (AIRarginine) and glucose (AIRglucose), and glucose potentiation of AIRarginine (delta AIRarginine/delta G) and two direct objective measurements (pancreatic insulin content [PIC] and quantitative beta-cell mass)--in adolescent male baboons (Papio anubis/cyanocephalus). We have correlated in vivo measurements obtained within 3 days after the animals were killed with in vitro estimates of PIC and beta-cell mass in 15 animals, (2 nondiabetic requiring insulin treatment and 13 after varying doses of streptozocin to induce degrees of beta-cell damage ranging from normoglycemia to severe hyperglycemia). There was a strong linear correlation between beta-cell mass and PIC (r = 0.79, P less than 0.001). Physiological measures of beta-cell function were significantly correlated with both PIC and beta-cell mass. The correlations between physiological measures and beta-cell mass were linear and intercepted the beta-cell mass axis at 0.15-0.2 g, suggesting that in vivo measures of beta-cell function approach 0 when there is still approximately 40-50% of the beta-cell mass detectable histologically. With PIC, the linear correlations intercepted the axes close to 0. These findings provide considerable validity to the measurements of beta-cell function used in preclinical IDDM in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

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.