No abstract

No abstract

Summary. The effects upon islet hormone secretion of highly purified preparations of secretin and of pancreozymin-cholecystokinin and of a crude gastrin-containing extract of hog antrum have been studied in acutely operated dogs. All three preparations were shown to cause a striking increase in insulin concentration in the pancreaticoduodenal venous plasma after their rapid endoportal injection in anesthetized dogs. With each hormone preparation, the peak in insulin secretion occurred 1 minute after injection, and a rapid decline was observed immediately thereafter. Whereas secretin and gastrin failed to alter significantly the pancreaticoduodenal venous glucagon or arterial glucose concentration, pancreozymin caused a dramatic rise in pancreaticoduodenal venous glucagon concentration, which reached a peak 3 minutes after injection, and hyperglycemia was noted to occur soon thereafter. Endoportal infusion of secretin and pancreozymin for 20 minutes caused responses that were sustained but qualitatively identical to the responses noted after rapid injection of the hormones. The beta-cytotropic effect of secretin was abolished by the infusion of epinephrine.These results could not be attributed to the small degree of contamination of the enteric hormone preparations with insulin or glucagon, and it would appear that secretin, pancreozymin, and probably gastrin have insulin-releasing activity and that pancreozymin has, in addition, glucagon-releasing activity.The demonstration that these three hormones possess insulin-releasing activity suggests that there is in the gastrointestinal tract a chain of betacytotropic hormones from antrum to ileum that is capable of augmenting insulin secretion as required for disposal of substrate loads. It is suggested that the existence of this "entero-insular axis" prevents high substrate concentrations that would otherwise follow ingestion of large meals were the insular response entirely a function of arterial substrate concentration. Introductionbe influenced by humoral factors of the gastro-

Although the precise effects of starvation upon the function of the alpha and beta cells of the islets of Langerhans are unknown, there is reason to suspect that they are profound. In dogs, for example, severe glucose need caused by insulininduced hypoglycemia (1, 2) and phlorizin-induced hypoglycemia (2) is associated with a marked increase in glucagon secretion. Furthermore, it has been demonstrated that, in starved rats, the extractable insulin of the pancreas is reduced (3); this leads to the concept that the impaired glucose tolerance of starvation may, in large part, be the result of reduced insulin secretion.A more complete understanding of the influence of glucose deprivation upon the function of the islet cells would clarify their role in the regulation of blood glucose disposition and homeostasis in health and in disease. Recently introduced immunochemical methods for the measurement of insulin (4, 5), and of glucagon (6, 7), made possible the following studies designed to determine the effect of total starvation upon the blood levels of these hormones in man. METHODS AND MATERIALSGlucagon assay. In order to enhance the sensitivity for measurement of endogenous glucagon in human serum, certain modifications of methods previously described (7) were introduced. These changes were found to be necessary, not only because of the lower concentrations of glucagon present in posthepatic blood as compared with that of the pancreatic venous effluent, obviously inaccessible in human studies, but also because of the non-

A B S T R A C T The effects of ingested and infused glucose upon circulating glucagon-like immunoreactivity (GLI) were compared in 14 triply catheterized conscious dogs. Within 60 min after the intraduodenal administration of 2 g/kg of glucose, the mean level of glucagon-like immunoreactivity in the vena caval plasma more than doubled, whereas after intravenous infusion of the same dose over a 90 min period no change in the mean vena caval level was observed; during glucose infusion mean glucagon-like immunoreactivity in the pancreatic venous effluent declined, suggesting that hyperglycemia suppresses rather than stimulates pancreatic glucagon secretion.To determine if the rise in glucagon-like immunoreactivity that occurs during glucose absorption was of pancreatic origin, the effect of pancreatectomy performed 1 hr after the intraduodenal administration of glucose was determined. Although circulating insulin disappeared after resection of the pancreas, the level of glucagon-like immunoreactivity continued to rise, establishing its extrapancrentic origin. In other experiments, measurements j. 'cagon-like immunoreactivity in plasma obtained simultaneously from pancreatico-