Abnormal Secretion of Insulin and Glucagon by the In Vitro Perfused Pancreas of the Genetically Diabetic Chinese Hamster

Frankel, Barbara J.; Gerich, John E.; Hagura, Ryoko; Fanska, R.; Gerritsen, G. C.; Grodsky, Gerold M.

doi:10.1172/jci107714

Cited by 69 publications

(51 citation statements)

References 30 publications

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“…In the normal hamsters, glucose plus arginine caused biphasic patterns of insulin and glucagon release (insulin second phase constant, glucagon second phase falling), whereas theophylline gave essentially constant second phase insulin and glucagon release [3,7]. Potassium caused rapid release of insulin and glucagon in the first phases, with little insulin and no glucagon in the second phases [7].…”

Section: Resultsmentioning

confidence: 99%

“…The diabetics' subnormal insulin responses to glucose plus arginine and to potassium could be due to subnormal islet insulin synthesis [9] and content [3,10,Gerritsen,personal communication]. However, because theophylline caused normal or greater than normal insulin release, the effectiveness of cyclic AMP and the process of exocytosis appear to be normal, and thus insulin release, at least in response to theophylline, appears to be unrelated to pancreatic content.…”

Section: Discussionmentioning

confidence: 99%

“…However, because theophylline caused normal or greater than normal insulin release, the effectiveness of cyclic AMP and the process of exocytosis appear to be normal, and thus insulin release, at least in response to theophylline, appears to be unrelated to pancreatic content. Alternatively, the excess glycogen seen in the diabetic B cell [11,12] may act as an intracellular source of glucose intermediates, and these metabolites may act synergistically with theophylline [3] to promote insulin release in the diabetic.…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatic perfusion was performed in vitro as described previously [3,4] except that the total perfusion flow rate was only 1.3 ml/ rain, the animals were not fasted before perfusion, and glucagon was assayed using Unger 30K or 04A antiserum. These two antisera gave identical results in our assays of glucagon release from normal rat pancreas in vitro.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 96%

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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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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

1982

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GLP‐1 Biology, Signaling Mechanisms, Physiology, and Clinical Studies

et al. 2011

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Glucagon and Glucagon‐like Peptide Production and Degradation

Kieffer

Hussain

Habener

2001

Comprehensive Physiology

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The sections in this article are: History Glucagon Glucagon‐like Peptides The Glucagon Superfamily of Peptide Hormones Tissue Distribution of Proglucagon Expression Pancreas Intestine Brain Proglucagon Biosynthesis Organization and Structure of the Proglucagon Gene Regulation of Glucagon Gene Expression Posttranslational Processing of Proglucagon Chemistry and Structure Regulation of Glucagon Secretion Overview Intracellular Signals Nutrients Endocrine/Paracrine Neural Pulsatility Regulation of Glucagon‐like Peptide‐1 Secretion Overview Intracellular Signals Nutrients Endocrine Neural Metabolism and Degradation Overview Renal Clearance Hepatic Clearance Degradation in the Circulation Biologically Active Fragments Physiological Actions Glucagon Glucagon‐like Peptide‐1 Glucagon‐like Peptide‐2 Mechanisms of Action Glucagon Glucagon‐like Peptide‐1 Glucagon‐like Peptide‐2 Human Disease Glucagon Glucagon‐like Peptide‐1 Glucagon‐like Peptide‐2

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Abnormal Secretion of Insulin and Glucagon by the In Vitro Perfused Pancreas of the Genetically Diabetic Chinese Hamster

Cited by 69 publications

References 30 publications

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

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

GLP‐1 Biology, Signaling Mechanisms, Physiology, and Clinical Studies

Glucagon and Glucagon‐like Peptide Production and Degradation

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