Acute effects of alloxan- and streptozotocin-induced insulin deficiency on somatostatin and glucagon secretion by the perfused isolated rat pancreatico-duodenal preparation

Abstract

Summary. The secretion of somatostatin and glucagon by the perfused rat pancreatico-duodenal preparation was examined in situ under control conditions and after the induction of acute insulin deficiency by alloxan or streptozotocin. A 10min 0.625 mmol/1 alloxan perfusion resulted in an immediate and transient increase in basal insulin and glucagon release and a slightly delayed and persistent increase in basal somatostatin secretion. The insulin responses to 16.7mmol/I glucose, 1 mmol/1 theophylline, and 19 mmol/l arginine alone or.in combination were virtually eliminated by atloxan treatment. Somatostatin secretion in response to the stimuli was completely inhibited or markedly attenuated. The glucagon-suppressive effect of glucose was unaltered by alloxan and the stimulatory effect of arginine was enhanced. Addition of 1 ~xg/ml porcine insulin to the perfusion medium did not modify the alterations in somatostatin and glucagon responses to arginine. Streptozotocin treatment 90 rain prior to the onset of perfusion resulted in changes in somatostatin, glucagon, and insulin responses to glucose and arginine similar to those of alloxan. The present results are consistent with an effect of alloxan and streptozotocin on the D cell similar to that on the B cell, namely, interference with a glucose-mediated effect on hormone secretion.Key words: Alloxan, perfusion, theophylline, streptozotocin, somatostatin, insulin, glucagon, rat, glucose, pancreas, arginine.Somatostatin is localized within the pancreas in secretory granules in D cells of the islets of Langerhans [1, 2] and its secretion is enhanced by glucose [3,4], theophylline [5,6], and glucagon [7]. Administration of exogenous somatostatin inhibits the release of insulin and glucagon [8,9]. These observations, together with those of D cell hyperplasia and hypertrophy and of increased pancreatic somatostatin-like immunoreactivity in streptozotocin-and alloxaninduced diabetes in the rat [10][11][12] and in human insulin-dependent diabetes [13], suggest that somatostatin exhibits an important role in the physiology of islet function and possibly in the pathophys.-iology of diabetes.It has recently been reported that plasma somatostatin-like immunoreactivity is elevated in alloxan diabetic dogs [14] and in streptozotocin diabetic rats [15] and that somatostatin secretion from the isolated perfused pancreas of alloxan diabetic rats is exaggerated in response to arginine [16]. In another study, by contrast, normal pancreatic somatostatin responses to arginine, isoproterenol and calcium and a diminished response to glucose were seen in streptozotocin diabetic dogs [17]. The present study was therefore undertaken to investigate further the acute effects of alloxan and streptozotocin on pancreatic somatostatin secretion in the isolated perfused rat pancreas. Materials and MethodsPancreases and attached segments of duodenum from overnight fasted male Sprague Dawley rats weighing 300-350 g, were perfused in situ by a previously described method [6]. All perfusions were. per...

Induction and Management of Diabetes Mellitus in the Pig

“…A similar finding has been reported using the perfused isolated rat pancreaticoduodenal preparation (Goto, Berelowitz and Frohman, 1981). It has been suggested that endogenous insulin, glucagon and somatostatin act locally within the islet to regulate each other's secretion.…”

Role of glucose and insulin in the dynamic regulation of glucagon release by the perfused rat pancreas

“…When the concentration of glucose was increased to 4.6 retool/1 for 23 min, the integrated output of insulin did not exceed 5.8 ng (or 3.2 mU/1). That glucose can inhibit glucagon release in the virtual absence of insulin has been documented previously by other investigators (3,(24)(25)(26)(27)(28).…”

“…The concept of a dual control of glucagon release by both glucose and insulin cannot be ruled out. In several studies performed in normal pancreatic tissue, no direct effect of exogenous insulin upon glucagon release could be observed [24,[28][29][30][31]. However, in the presence of glucose, exogenous insulin was found to decrease glucagon output in pancreatic tissue removed from streptozotocin-treated guinea pigs and rats [31][32][33].…”

Pentamidine, a new diabetogenic drug in laboratory rodents

“…Our data suggest that pentamidine exerts two distinct influences on the B cells: (1) an impairment of B cell response to glucose and arginine detectable as early as 1 h after exposure to the drug, and (2) a cytolytic process strongly suggested by 5tChromium release, the Trypan blue test and excessive release of insulin in non-stimulatory conditions. This leakage may be similar to that observed when alloxan and streptozotocin are used [14,15], albeit less acute in the case of pentamidine than with alloxan [15]. Streptozotocin, added to dispersed islet cells incubated in vitro, induces a pattern very similar to that obtained with pentamidine, i. e. IRI release in non-stimulatory conditions and no response to glucose + theophylline (data not shown).…”