Somatostatin: Hypothalamic Inhibitor of the Endocrine Pancreas

Koerker, Donna J.; Ruch, W.; Chideckel, Elliott W.; Palmer, Jerry P.; Goodner, Charles J.; Ensinck, John W.; Gale, C

doi:10.1126/science.184.4135.482

Cited by 530 publications

(192 citation statements)

References 12 publications

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“…Under the present experimental conditions, however, somatostatin remarkably reduced the glucose-induced insulin secretion in anesthetized dogs. Somatostatin has been shown to inhibit insulin secretion both in vivo and in vitro (22)(23)(24)(25). Doses of diltiazem used in the present experiments were sufficient to produce hemodynamic effects.…”

Section: Discussionmentioning

confidence: 55%

Effect of diltiazem on insulin secretion

Yamaguchi

Akimoto

Nakajima

et al. 1979

Japanese Journal of Pharmacology

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Abstract-Effect of diltiazem on insulin secretion was investigated in the perfused rat pancreas. Experiments were also carried out in anesthetized dogs and conscious rats with and without glucose loading.In the perfused rat pancreas, diltiazem reduced both glucose and tolbutamide-induced insulin secretion and these effects of diltiazem were reversed with removal of the compound. Inhibition of the glucose-induced insulin secretion caused by diltiazem was counteracted by increasing the concentration of calcium ion. In experiments on intact animals, diltiazem at vasoactive doses produced no significant influence on the basal level of plasma insulin or glucose-induced insulin secretion.These data taken together with findings in previously reported work suggest that diltiazem reduces insulin secretion from pancreatic B-cells in vitro possibly by the calcium-antagonistic property, while the compound exhibits practically no inhibitory action on the insulin secretion in vivo.In a preceding paper (1), it was shown that in isolated islets of Langerhans from rats, diltiazem produced a concentration-dependent inhibition of the release of insulin following stimulation with glucose. This inhibitory effect of diltiazem was antagonized with increasing concentrations of extracellular calcium ion. We suggested that diltiazem may suppress the glucose-induced insulin secretion by reducing free calcium ion concentration in B-cells.In the present study, the time course for change in insulin secretion from rat pancreas was followed using a perfusion method and the dynamic aspects of the inhibitory effect by diltiazem were studied. In vivo effects of diltiazem on the insulin secretion were also studied in dogs and rats with and without glucose loading. MATERIALS AND METHODS1. Perfusion of rat pancreas: The perfused rat pancreas was prepared according to the method described by Sussman et al. (2) with slight modification. Male Sprague-Dawley rats (about 450 g) were anesthetized with sodium pentobarbital (50 mg/kg i.p.) and the abdominal cavity was opened. All abdominal vessels except for the superior mesenteric artery and celiac axis were ligated and cut. A portion of the duodenum tightly adhering to the pancreas was left intact. The thoracic aorta was cannulated to a point just superior of the celiac axis and the perfusate was allowed to flow through the pancreas and a portion of the small intestine. The effluent was continuously collected through a cannulated portal vein at one to two min intervals. At the end of the experiments, the perfusion circuit was confirmed to be complete by perfusion with Evans blue. The perfusate was Krebs-bicarbonate

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Section: Discussionmentioning

confidence: 55%

Effect of diltiazem on insulin secretion

Yamaguchi

Akimoto

Nakajima

et al. 1979

Japanese Journal of Pharmacology

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“…Finally, reduction of insulin release by the tumour in response to leucine plus theophylline was achieved using either adrenaline or somatostatin. Both agents inhibit insulin secretion by islet tissue [36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Insulin secretion by a transplantable rat islet cell tumour

et al. 1981

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Summary. Investigation of the subcellular and molecular components of insulin secretion has been made difficult by the small quantities of material available. The recent development of a transplantable rat islet cell tumour of high insulin content and state of differentiation suggested a system more amenable to analysis. To validate the tumour as a model of secretion we have studied its release of insulin. In acute experiments in vitro immunoreactive insulin release was increased by leucine, glucagon, theophylline and dibutyryl cyclic AMP, though not by glucose. Leucine (20 mmol/1) plus theophylline (5 mmol/1) caused an abrupt, sustained and rapidly reversible stimulation of two-to fivefold. The response was inhibited by antagonists of cellular oxidative phosphorylation (cyanide, 2,4--dinitrophenol, antimycin A), calcium flux (EGTA, verapamil, Mg2 § calmodulin (trifluoperazine), microtubules (vinblastine, colchicine) and by adrenaline and somatostatin. These findings suggest that the tumour secretes insulin by an exocytotic mechanism similar to that of normal islet tissue. Key words: Islet cell tumour, B cell, insulin secretionThe pancreatic B cell has proved difficult to investigate at the subcellular and molecular levels. The classical strategy of subcellular fractionation, purification and reassembly has been greatly hindered by the shortage of starting material [3,4]. In this context the description recently of a transplantable rat islet cell tumour is of considerable interest. The tumour contains large amounts of insulin and consists predominantly of well-granulated cells the morphology of which closely resembles that of rat B cells [1,2].That this islet cell tumour might offer a largescale model of insulin secretion is an attractive possibility. Realisation of this potential, however, depends upon establishing that the tumour is indeed capable of the exocytosis of insulin. We here report a series of experiments in which the characteristics of insulin release by the turnout were defined. The effect of putative secretagogues, the dynamics of insulin release, and the influence of potentiators and inhibitors of secretion are described. Materials and MethodsThe islet cell tumour [1, 2] was maintained by serial subcutaneous transplantation within a colony of inbred albino NEDH strain rats [2]. BuffersTissue was handled in a Krebs Ringer solution [5] containing NaC1 115mmol/1, KC1 5.0mmol/1, NaI-ICO 3 24mmol/1, MgC12 1.0 mmol/1 and CaC12 2.5 mmol/1, freshly equilibrated with 5% CO 2 95% 02. Except where specified glucose 2.8 mmol/l, bovine plasma albumin (Armour Pharmaceuticals, Eastbourne, UK) 1.0 mg/ml, and 5.0 mmol/1 each of sodium pyruvate, monosodium glutamate and disodium fumarate were included (using 95 mmol/l NaC1 to maintain the final sodium ion concentration at 139 mmol/ 1). When individual experiments required further additions the osmolality of control buffers was balanced using sucrose.Chemicals were purchased from Fisons Scientific Apparatus, Loughborough, UK and British Drug House Chemicals, Poole,...

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“…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.…”

mentioning

confidence: 91%

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

1981

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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...

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Somatostatin: Hypothalamic Inhibitor of the Endocrine Pancreas

Cited by 530 publications

References 12 publications

Effect of diltiazem on insulin secretion

Effect of diltiazem on insulin secretion

Insulin secretion by a transplantable rat islet cell tumour

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

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