The gamma-aminobutyric acid (GABA) concentration of pancreatic islets in rats treated with streptozotocin (STZ) and of human insulinoma tissue was studied. Seven hours after the administration of 65 mg/kg body weight of STZ, a distinct increase in serum insulin concentration and at the same time a decrease in blood glucose level were seen. Twenty-four hours after the injection of STZ, however, the level of serum insulin decreased much, whereas that of blood glucose increased considerably. On the other hand, the GABA concentration of the islet was reduced dramatically to about one-tenth the control level after both 7 and 24 h. The histologic investigations of the islets revealed the destruction of B cells but no changes in A and D cells 7 and 24 h after the treatment of STZ. Nerve fibers and nerve endings in the islets were preserved intact all through the study. The GABA and insulin contents of the two cases of human insulinoma were determined. One insulinoma, which was compactly occupied with B cells according to its histologic features, contained a high concentration of GABA. The other tumor, having a rather sparse distribution of B cells in it as compared with the former case, possessed a lower concentration of GABA, but it was still high compared with that of its surrounding tissues. The present observations indicate that a large amount of GABA is available in the B cells of the pancreatic islets.

In order to clarify the physiologic role of somatostatin in insulin release, rat pancreatic islets treated by somatostatin antiserum were incubated in media containing various concentrations of glucose. Insulin release from antiserum-treated islets was significantly elevated above that from nontreated ones at 3.3 and 8.3 mM glucose, while the former was not different from the latter at 16.7 mM glucose. It is suggested that somatostatin plays an important role in the regulation of insulin release in the physiologic range of glucose concentration.

257 Schade, D.S., R.P. Eaton: Modulation of fatty acid metabolism by glucagon in man. 11. Effects in insulin-deficient diabetics. Diabetes 24: 509-515 (1975) Schade, D.S., R.P. Eaton: The contribution of endogenous in man. Diabetologia 11: 555-559 (1975) Sherwin, R.S., M. Fisher, R. Hendler, P. Felig: Hyperglucagonemia and blood glucose regulation in normal, obese dand diabetic subjects. N.EngLJ.Med. 294: 455 (1976)Requests for reprints should be addressed to: SummaryThe insulin responsiveness of the isolated islets to various agents was studied in one-day-old and adult rats in an in vitro incubation system.The responsiveness to 16.7 mM glucose and 16.7 mM glucose plus 1.3 mM theophylline was lower in younger age rats, while that to 16.7 mM glucose plus 10.0 mM adenosine was not different between both age groups. On the other hand, the relative ATP concentration, which implied the ratio of ATP content per unit weight of islet induced by various agents to that by 3.3 mM glucose, did not increase so much in one-day-old rat islets as in adult ones when they were incubated in 16.7 rnM glucose and in 16.7 mM glucose plus 1.3 mM theophylline, while it showed no significant difference between both groups when they were incubated in 16.7 mM glucose plus 10.0 mM adenosine.These observations suggest that rat islets might respond to not only the increase of cyclic AMP but also that of relative ATP concentration, releasing insulin, and that newborn islets might not be equipped with the mature adenyl cyclase-cyciic AMP system as contrasted to adult ones.

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