The effects of glucose, amino acids, pancreozymin cholecystokinin, and tolbutamide upon the release of immunoreactive somatostatin (IRS) from the isolated perfused pancreas were studied. In 7 experiments in which glucose was perfused either at a concentration of 100 or 350 mg/dl or at 25 mg/dl, IRS levels were significantly greater at the higher glucose concentrations. In 3 dose response experiments in which the perfusing glucose concentration was increased at 30 min intervals from an initial concentration of 25 mg/dl to a final concentration of 300 mg/dl, progressive increases in IRS release were noted at glucose concentrations of 100 mg/dl and above. Perfusion of a 20 mM mixture of 10 amino acids also elicited a prompt and significant biphasic IRS rise in each of 6 experiments. In 5 experiments, 20 mM leucine evoked a similar response in mean IRS. Perfusion with 0.075 Ivy U/ml of pancreozymin cholecystokinin, with or without the presence of a 1 mM 10 amino acid mixture, elicited a prompt rise in IRS with a pattern resembling that of insulin in a total of 6 experiments. Tolbutamide (0.75 mg/min) also stimulated IRS release in 5 of 6 challenges. The IRS responses to nutrients and to pancreozymin and their similarity to the insulin responses raise the possibility that, like insulin, pancreatic somatostatin may have an endocrine role related to nutrient homeostasis.
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