LACK OF EFFECT OF CS-045, A NEW ANTIDIABETIC AGENT, ON INSULIN-SECRETION IN THE REMNANT PANCREAS AFTER 90-PERCENT PANCREATECTOMY IN RATS

We assessed the effect of CS-045, a new hypoglycemic agent, on B-cell function in partially pancreatectomized rats. At the age of 4 weeks, m ale Wistar rats were subjected to 90% pancreatectomy (Px). For 2 weeks starting at 6 weeks after surgery the Px rats were treated with CS-04 5 (CS rats) mixed with chow pellets in a proportion of 0.2% (w/w). To compare the efficacy of CS-045 with that of insulin therapy, an osmoti c pump was implanted to release insulin (1.2 units/day) into the intra peritoneal cavity of the Px rats (Is rats). Plasma glucose levels in t he CS and Is rats were significantly lower than in the control Px rats ; however, no marked improvement in plasma glucose or insulin levels w as observed in glucose tolerance test (2 g/kg, i.p.) in the CS rats. I nsulin secretion by the isolated perfused pancreas in response to 16.7 mM glucose showed a biphasic pattern, but was slightly reduced in the Pr and CS rats compared with the Is rats. Insulin secretion induced b y 19 mM arginine was unaffected by the treatment. The insulin content of the CS rats was significantly greater than in the Pr and Is rats. H istological observations suggested regranulation of the pancreatic isl ets of the CS rats. B-cell areas within the islet were restored to nor mal levels in the Cs and Is rats. These findings indicate that the hyp oglycemic effect of CS-045, which is not mediated by insulin secretion from the residual pancreas, prevents destruction of the islet.