Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster.

Hereditary insulin-deficient diabetes mellitus occurs in certain sublines of nonobese Chinese hamsters. Several characteristics of this syndrome are similar to those seen in insulin-deficient human diabetics. Therefore, to characterize pancreatic islet function, dynamic insulin and glucagon release from normal and nonketotic diabetic hamster pancreases in response to glucose (300 mg/100 ml) and theophylline (10 mM), infused singly and together, was studied in vitro.20-min glucose infusions of normal hamster pancreases caused biphasic insulin release, consisting of a rapid first peak and a gradually rising second phase, similar to that reported for man in vivo. Both phases were significantly reduced in the diabetic pancreases. Theophylline alone stimulated similar nonphasic insulin release in both the normal and the diabetic pancreases. Glucose and theophylline together caused greater insulin release than either stimulant alone in both normals and diabetics; however, the diabetic response was still subnormal. Glucose suppressed glucagon release from normal pancreases; suppression was significantly impaired in diabetics. Theophylline stimulated nonphasic glucagon release in both the normals and diabetics. Glucose partially suppressed the theophylline-stimulated release in both groups.Insulin/glucagon molar ratios of the diabetics were consistently subnormal, although individual hormone levels often overlapped into the normal range. IN SUMMARY, THE PANCREASES OF GENETICALLY DIABETIC CHINESE HAMSTERS PERFUSED IN VITRO SHOWED: (a) decreased first and second phase insulin release in response to glucose-containing stimuli-only partially ameliorated by theophylline-, and (b) impaired suppression of glucagon in response to glucose, resulting in (c) a decreased insulin/glucagon molar ratio. These data support the suggestion that both alpha and beta cells of diabetic pancreases may be insensitive to glucose.

[1]  J. Gerich,et al.  Lack of Glucagon Response to Hypoglycemia in Diabetes: Evidence for an Intrinsic Pancreatic Alpha Cell Defect , 1973, Science.

[2]  D. Porte,et al.  The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor. , 1973, The Journal of clinical investigation.

[3]  P. Felig,et al.  Evaluation of alpha-cell function by infusion of alanine in normal, diabetic and obese subjects. , 1973, The New England journal of medicine.

[4]  G. Grodsky,et al.  In vitro inhibition of pancreatic glucagon secretion by diphenylhydantoin. , 1972, The Journal of clinical endocrinology and metabolism.

[5]  G. Grodsky,et al.  A threshold distribution hypothesis for packet storage of insulin and its mathematical modeling. , 1972, The Journal of clinical investigation.

[6]  G. Grodsky,et al.  A Threshold Distribution Hypothesis for Packet Storage of Insulin: II. Effect of Calcium , 1972, Diabetes.

[7]  W. A. Müller,et al.  Abnormal Alpha Cell Function in Diabetics Response to Insulin , 1972, Diabetes.

[8]  E. Cerasi,et al.  Decreased Sensitivity of the Pancreatic Beta Cells to Glucose in Prediabetic and Diabetic Subjects: A Glucose Dose-Response Study , 1972, Diabetes.

[9]  W. A. Müller,et al.  The effect of experimental insulin deficiency on glucagon secretion. , 1971, The Journal of clinical investigation.

[10]  R. Unger.  Glucagon physiology and pathophysiology. , 1971, The New England journal of medicine.

[11]  W. A. Müller,et al.  Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. , 1970, The New England journal of medicine.

[12]  W. A. Müller,et al.  Studies of pancreatic alpha cell function in normal and diabetic subjects. , 1970, The Journal of clinical investigation.

[13]  A. Renold,et al.  The pathogenesis of diabetes mellitus. Possible usefulness of spontaneous hyperglycemic syndromes in animals. , 1970, California medicine.

[14]  E. Cerasi,et al.  The Effect of an Adenosine - 3', 5' - Monophosphate Diesterase Inhibitor (Aminophylline) on the Insulin Response to Glucose Infusion in Prediabetic and Diabetic Subjects , 1969, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[15]  D. Kipnis.  Insulin secretion in diabetes mellitus. , 1968, Annals of internal medicine.

[16]  G. Grodsky,et al.  Dynamics of insulin secretion by the perfused rat pancreas. , 1968, Endocrinology.

[17]  G. Grodsky,et al.  Effect of pulse administration of glucose or glucagon on insulin secretion in vitro. , 1967, Metabolism: clinical and experimental.

[18]  G. Grodsky,et al.  Stimulation of insulin release by glucagon in noninsulin-dependent diabetics. , 1966, Metabolism: clinical and experimental.

[19]  G. Yerganian,et al.  Spontaneous Hereditary Diabetes Mellitus in the Chinese Hamster (Cricetulus Griseus): III. Maintenance of a Diabetic Hamster Colony With the Aid of Hypoglycemic Therapy , 1961, Diabetes.

[20]  G. Grodsky,et al.  An immunochemical assay of total extractable insulin in man. , 1960, The Journal of clinical investigation.

[21]  G. Yerganian,et al.  Spontaneous Hereditary Diabetes Mellitus in Chinese Hamster (Cricetulus griseus). 1. Pathological Findings.∗ † , 1959, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[22]  G. Grodsky,et al.  Paper Chromatography of Insulin , 1956, Nature.

[23]  W. A. Müller,et al.  Hyperglucagonemia in diabetic ketoacidosis. Its prevalence and significance. , 1973, The American journal of medicine.

[24]  J. Gerich,et al.  Abnormalities of glucagon in diabetic syndromes: Influence of obesity and response to oral glucose tolerance test (OGTT) , 1973 .

[25]  A. Chang.  INSULIN SYNTHESIS AND SECRETION BY ISOLATED ISLETS OF SPONTANEOUSLY DIABETIC CHINESE HAMSTERS , 1970 .