The object of this project is to study the role of islet peptides in the regulation of feeding behavior and body weight in baboons, and to evaluate the role of autonomic control of the endocrine pancreas to changes of glucose homeostasis during stress in dogs. In baboons the hypothesis will be tested that CSF hormone concentrations of pancreatic insulin comprises a feedback system for the regulation of food ingestion which is sensitive to relative adiposity. The effect of altered CSF insulin levels on feeding behavior will be studied in chronic unanesthetized free-feeding baboons. The sensitivity of food suppression by somatostatin and cholecystokinin to CSF insulin level alterations will be evaluated. A method for a sampling of CSF is proposed and the concentration of CSF insulin will be measured during changes in eating behavior induced by starvation, experimental obesity, and diabetes mellitus. Uptake of circulating peptides into CSF will be measured and rates of turnover estimated. The ability of intravenous nutrients to regulate feeding behavior will be estimated and correlated with changes of CSF peptide concentrations. In dogs, insulin, glucagon an somatostatin secretory rates and concentrations will be determined from the pancreaticoduodenal vein in vivo using an extracorporeal flow system for evaluation of endocrine pancreatic blood flow. The role of autonomic control of the islet and its mechanisms will be evaluated during pancreatic nerve stimulation. Hyperglycemia and changes in endocrine pancreatic function will be determined during four experimental stresses (glucopenia, hypoxia, hypothermia and acidosis). The relative stimulation of the autonomic nerves to the adrenal medulla and autonomic nerves to the endocrine pancreas will be estimated during these stresses by measurement of pancreaticoduodenal and peripheral norepinephrine and epinephrine concentrations. The importance of this neural islet regulation to stress hyperglycemia will then be assessed by pancreatic denervation, adrenalectomy, and islet hormone replacement.
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