Investigations of the control of pancreatic somatostatin secretion and its possible role as a local regulator of insulin and glucagon secretion will be extended and now also include evaluation of mechanisms by which somatostatin may inhibit insulin and glucagon secretion and characterization of somatostatin release from pancreases of animals with genetic and experimentally-induced diabetes mellitus: I. Effects of selected substrates, hormones, neurotransmitters, cations, and inhibitors of islet metabolism on somatostatin release from perfused dog pancreases will be correlated with simultaneous changes in insulin and glucagon secretion. II. Somatostatin binding to purified islet plasma membranes and cytosol protein(s), and the effects of somatostatin on calcium45 fluxes, cAMP and cGMP levels, and H3-glucose metabolism of incubated rat islets will be studied. III. Release of somatostatin, insulin and glucagon from perfused pancreases of genetically diabetic OBOB and DBDB mice and of experimentally diabetic dogs and rats will be correlated and compared with hormone release in matched non-diabetic animals and in insulin-treated diabetic animals.