Mechanism of glucose-induced insulin secretion.

Hedeskov, C. J.

doi:10.1152/physrev.1980.60.2.442

Cited by 432 publications

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“…A number of studies have suggested that elevations in intracellular CAMP produce an increased secretion of insulin from B-cells [ 1,2], but there is still some uncertainty as to the importance of CAMP in the B-cell secretory response [1,2,8,9]. In general, the majority of available experimental evidence suggests that CAMP does not initiate in-sulin secretion, but acts to modulate the secretory response to initiators of secretion such as glucose [2], perhaps by direct actions on Ca2+ fluxes into [15] or within [ 161 the B cell or, alternatively, by changing the sensitivity of the exocytotic mechanisms to Ca2+ [17-191. In this study the u;e of electrically permeabilised islets ensured that intracellular Ca2+ could be fixed at known and pre-determined concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have shown that insulin release is enhanced in the presence of analogues of CAMP, or by increasing intracellular CAMP using agents which activate adenylate cyclase or inhibit phosphodiesterases ([1,2,8] for references). Several hormones and neurotransmitters which affect insulin secretion are thought to act by receptormediated alteration of adenylate cyclase activity [3,5], and glucose or other metabolic secretagogues can elevate intracellular CAMP concentrations [2,9], perhaps as a response to increases in cytosolic Ga" [2, 8,9].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high‐voltage discharge

1986

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Adenosine 3',5-cyclic monophosphate (CAMP) was shown to stimulate ins&in secretion from electrically permeabilised islets of Langerhans incubated in Ca2+/EGTA buffers. CAMP-induced insulin secretion occurred in the presence of either sub-stimulatory (50 nM) or stimulatory (> 100 nM) concentrations of Ca2+.Similar effects on secretion were obtained in response to I-bromo-CAMP (8-Br-CAMP) or the phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine. Forskolin (0.2-20 PM) increased adenylate cyclase activity and enhanced insulin secretion from the ~~eabili~ islets. These results suggest that, in electrically permeabilised islets, CAMP-indu~d insulin secretion is not dependent on changes in cytosohc Ca2+. Insulin secretion (Islets of Langerhans)Electrical permeabilization cyclic AMP Forskolin Isobutylmethylxanthine

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high‐voltage discharge

1986

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“…The secretagogues used in this study were chosen on the basis of their abilities to induce insulin and glucagon release and their presumed mechanisms of action. Glucose plus arginine causes metabolic events affecting glycolysis, the Krebs' cycle, ATP, hydrogen ion concentration, NADPH, membrane depolarization and changes in membrane fluxes of calcium in the B cell [8]. Theophylline presumably elevates cyclic AMP and changes intracellular calcium ion levels, while potassium acts more distally on membrane polarization.…”

Section: Discussionmentioning

confidence: 99%

Insulin and glucagon release in the diabetic Chinese hamster: Differences among inbred sublines

1982

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Summary. Release of insulin and glucagon from perfused pancreases in vitro of 40 normal male and female Chinese hamsters (from one inbred subline) and 110 male and female diabetic hamsters (from three inbred sublines) was measured in response to glucose plus arginine, theophylline alone, or potassium alone, in order to determine if differences in hormone secretion exist among different diabetic sublines. Glucose plus arginine and potassium produced subnormal insulin responses in all three diabetic sublines, whereas theophylline induced 'normal' or above normal insulin responses. Excessive glucagon release was consistently seen in only one diabetic subline. The female normal animals showed greater insulin release than the male normal hamsters in response to glucose plus arginine. This sex difference was not seen in the diabetic animals. Key words:Chinese hamster, diabetes model, glucagon excess, glucagon release, insulin deficiency, insulin release, potassium, insulin secretion, theophylline.Certain inbred sublines of Chinese hamsters (Cricetulus griseus) spontaneously develop an insulin-deficient, non-obese type of diabetes mellitus with many sequelae similar to those seen in human diabetes [1,2]. Previous studies [3,4] have shown that the perfused pancreases of diabetic hamsters have subnormal insulin and excessive glucagon responses to glucose stimulation, excessive glucagon responses to arginine, but normal responses to theophylline. However, those studies did not compare the differences among specific diabetic sublines nor between males and females. In the last few years, several sublines have become more highly inbred, and differences in pancreatic and plasma levels of insulin and glucagon among different diabetic sublines have been observed [1, personal communication G.C.Gerritsen, Upjohn, Kalamazoo, Michigan, USA]. No morphological or biochemical studies which might explain the differences in pancreatic and plasma hormones among diabetic sublines have been published. Therefore, to characterize the defect(s) in pancreatic hormone secretion in the diabetic hamster, the effects of three different secretagogues were studied on insulin and glucagon release from the perfused pancreases of hamsters from one inbred normal and three different inbred diabetic sublines. The stimuli were as follows: a combination of glucose (low concentration) plus arginine, theophylline alone, and potassium alone. These particular secretagogues were chosen because they stimulate both insulin and glucagon release and because each is believed to induce insulin release by a different, though related mechanism, i.e. through metabolism, elevation of intracellular cyclic AMP and calcium, and membrane depolarization, respectively. Materials and MethodsAdult Chinese hamsters from one inbred normal (M) and three inbred diabetic (L, X, and Z) sublines were obtained from the Chinese Hamster Program Project colony at Kalamazoo, Michigan, USA [5]. It appears that these three diabetic sublines have subnormal pancreatic insulin, low and variable p...

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“…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.…”

Section: Abstract: Islet Cell Tumour B Cell Insulin Secretionmentioning

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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Mechanism of glucose-induced insulin secretion.

Cited by 432 publications

References 0 publications

Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high‐voltage discharge

Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high‐voltage discharge

Insulin and glucagon release in the diabetic Chinese hamster: Differences among inbred sublines

Insulin secretion by a transplantable rat islet cell tumour

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