Glucagon Secretion from the Perfused Pancreas of Streptozotocin-treated Rats

One hour following intravenous streptozotocin, rat pancreases were perfused in situ, and , in contrast to saline-injected controls a marked decrease of insulin secretion was observed. In these streptozotocin-treated animals, baseline glucagon secretion was enhanced when the perfusate glucose concentration was either 80 mg./100 ml. or 300 mg./100 ml. In addition there was hypersecretion of glucagon in response to arginine. Exogenous insulin (20,000 μU./ml.) could suppress glucagon secretion when endogenous secretion was plentiful. Baseline and arginine-stimulated glucagon secretion of the streptozotocin treated animals was not suppressed by large amounts of glucose and insulin to the degree seen in control animals. The glucagon rise in response to an abrupt fall of glucose from 80 mg./100 ml. to 25 mg./100 ml. was not significantly higher in the control group than in the streptozotocin group. The results seen with epinephrine were in sharp contrast to those found with arginine. Epinephrine-stimulated glucagon secretion was not enhanced in the streptozotocin group. In addition, epinephrine-induced secretion could be suppressed by exogenous insulin in both the control and streptozotocin groups. The differences may be secondary to differences of endogenous insulin secretion. The present results are compatible with the hypothesis that local insulin secretion can exert a significant suppressive effect upon the alpha cell and that the inhibition of glucagon secretion by glucose is partially mediated by this mechanism. Furthermore, anomalous local insulin secretion may contribute to the abnormal glucagon secretion of diabetes mellitus.

[1]  P. Raskin,et al.  Effect of insulin-glucose infusions on plasma glucagon levels in fasting diabetics and nondiabetics. , 1975, The Journal of clinical investigation.

[2]  M. Dubois.  Immunoreactive somatostatin is present in discrete cells of the endocrine pancreas. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. Tsalikian,et al.  Plasma glucagon and alanine responses to acute insulin deficiency in man. , 1975, The Journal of clinical endocrinology and metabolism.

[4]  L. Orci,et al.  Glucagon: role in the hyperglycemia of diabetes mellitus. , 1975, Science.

[5]  M. Haymond,et al.  Insulin and glucose as modulators of the amino acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. , 1975, The Journal of clinical investigation.

[6]  G. Weir,et al.  Somatostatin inhibition of epinephrine-induced glucagon secretion. , 1974, Endocrinology.

[7]  G. Weir,et al.  Glucagon secretion from the perfused rat pancreas. Studies with glucose and catecholamines. , 1974, The Journal of clinical investigation.

[8]  M. Vranic,et al.  Increased “Glucagon Immunoreactivity” in Plasma of Totally Depancreatized Dogs , 1974, Diabetes.

[9]  R. Guillemin,et al.  Effects of somatostatin on plasma glucose and glucagon levels in human diabetes mellitus. Pathophysiologic and therapeutic implications. , 1974, The New England journal of medicine.

[10]  S. Woods,et al.  Neural control of the endocrine pancreas. , 1974, Physiological reviews.

[11]  G. Grodsky,et al.  Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster. , 1974, The Journal of clinical investigation.

[12]  C. J. Goodner,et al.  Somatostatin: Hypothalamic Inhibitor of the Endocrine Pancreas , 1974, Science.

[13]  R. Unger,et al.  The effect of insulin on the alpha-cell response to hyperglycemia in long-standing alloxan diabetes. , 1974, The Journal of clinical investigation.

[14]  S. Bloom,et al.  The role of the autonomic innervation in the control of glucagon release during hypoglycaemia in the calf , 1974, The Journal of physiology.

[15]  K. Buchanan,et al.  Insulin Control of Glucagon Release From Insulin-deficient Rat Islets , 1973, Diabetes.

[16]  K. Buchanan,et al.  Glucagon Release from Isolated Pancreas in Streptozotocin-treated Rats , 1973, Diabetes.

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

[18]  J Roth,et al.  Insulin-receptor interaction in the obese-hyperglycemic mouse. A model of insulin resistance. , 1973, The Journal of biological chemistry.

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

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

[21]  N. Katsilambros,et al.  Action of streptozotocin on insulin and glucagon responses of rat islets. , 1970, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

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

[23]  F. Wolff,et al.  A Rat Pancreas-Small Gut Preparation for the Study of Intestinal Factor(s) and Insulin Release , 1969, Diabetes.

[24]  F. Matschinsky,et al.  Metabolism of glucose in the islets of Langerhans. , 1968, The Journal of biological chemistry.

[25]  D. Porte,et al.  The effect of epinephrine on immunoreactive insulin levels in man. , 1966, The Journal of clinical investigation.

[26]  V. Marks,et al.  PROMOTION OF INSULIN SECRETION BY GLUCAGON. , 1965, Lancet.

[27]  P. J. Randle,et al.  Regulation of insulin secretion studied with pieces of rabbit pancreas incubated in vitro. , 1964, The Biochemical journal.