Somatostatin, glucagon, and insulin secretion from perfused pancreas of BB rats

We reported previously that pancreatic somatostatin and glucagon content and D and A cells are reduced in spontaneously diabetic BB rats while portal plasma levels of these hormones are elevated but normalized by insulin therapy. Presently, we have characterized the basal and stimulated (glucose, theophylline, arginine) release of islet hormones from perfused pancreases of three groups: nondiabetic, untreated diabetic, and insulin-treated diabetic rats. Maximal glucagon and somatostatin release were significantly reduced in untreated diabetics. Treatment normalized glucagon but further reduced somatostatin secretion. Thus, hyperglucagonemia and hypersomatostatinemia cannot result from pancreatic hypersecretion but are of extrapancreatic (probably gut) origin. A theophylline-induced paradoxical inhibition of somatostatin secretion that was normalized by insulin was found in insulin-openic diabetic rats. This likely represents a secondary effect of insulin deficiency. One animal with the rare finding of spontaneous recovery from insulin-dependent diabetes was characterized as normoglycemic, hypoinsulinemic, hypersomatostatinemic, and normoglucagonemic. Normal basal and hyperglycemic insulin release was exhausted by more potent secretagogues. Somatostatin release was markedly exaggerated, whereas secretagogues had no significant effect on elevated basal glucagon output.