Effects of Tolbutamide on Insulin and Glucagon Secretion of the Isolated Perfused Rat Pancreas

Abstract

Insulin and glucagon release in the isolated perfused rat pancreas was measured after stimulation with tolbutamide. The perfusion medium contained either 5.5 mM of glucose or was glucose free. During the first ten min of perfusion with tolbutamide, insulin output rose rapidly while glucagon release was signiticantly depressed After aperiod of prolonged stimulation glucagon began rising again but did not return to initial levels. Following destruction of insulin-producing Bcells by streptozotocin, tolbutamide still caused identical inhibition of glucagon secretion, as in the presence of intact islets. A signiflcant inverse relationship between insulin and glucagon output seemed to be established Yet, despite the fact that considerably higher insulin levels were kept in the presence of S.S mM glucose in the perfusate, tolbutamide effected about the same depression of glucagon quantitatively

Effects of Streptozotocin on Liver Composition and Blood Glucose, Ketone Bodies and Insulin in the Fed and Fasted Male Rat

“…The fact that several of these alterations in the fasted animals disappeared a few minutes after the administration of insulin could be in agreement with this interpretation [6,10]. The possibility exists too, that the observed changes in the streptozo tocin-treated rats were also facilitated by parallel variations in other endo crine sites such as an elevation of circulating glucagon levels, as reported by K atsilambros et al [14] after the treatment with streptozotocin in vivo, although this was not confirmed under in vitro conditions [16] and deserves further investigation. The concomitant effects of low insulin and high glucagon levels would also be inducing not only a hightened hepatic gluco-neogenesis and decreased peripheral glucose utilization but also an enhanced glycogenolysis, all of which would be contributing to the hyperglycemia and the low hepatic glycogen concentration found here in the fed rats treated with streptozotocin.…”

Effect of glucose/sulfonylurea interaction on release of insulin, glucagon, and somatostatin from isolated perfused rat pancreas.

“…This observation probably explains previous reports suggesting either a stimulatory or inhibitory effect of sulfonylureas on glucagon release (6)(7)(8). The inhibition of glucagon release by glibenclamide, which was parallel to the phase of rapid increase in somatostatin release, implies that somatostatin may have mediated the inhibition of glucagon release.…”

“…Their effect on insulin release is dependent upon the prevailing glucose concentration (4,5). There are contradictory reports regarding the effect of sulfonylureas on glucagon release: they have been considered to either stimulate (6) or inhibit this function (2,7,8).…”

Characterization of the Effects of Arginine and Glucose on Glucagon and Insulin Release from the Perfused Rat Pancreas

“…Indeed, whether insulin is required for, or contributes appreciably to, the suppressive effect of glucose on glucagon secretion (50) is open to question. In studying glucagon secretion from perfused pancreases of rats made diabetic with streptozotocin, Laube et al, found no effect of infused insulin on glucagon release (42), and Pagliara et al found that glucose was able to inhibit glucagon release in the absence of demonstrable insulin secretion (44). In general, studies showing a suppressive effect of insulin on glucagon secretion (50) have been performed in vivo where effects of insulin other than those directly on the alpha cell may be operative.…”