Autonomic control of pancreatic polypeptide and glucagon secretion during neuroglucopenia and hypoglycemia in mice.

Neural control of pancreatic polypeptide (PP) release has not been previously investigated in the mouse. In addition, it is not known to what extent increased glucagon secretion during hypoglycemia in mice is neurally mediated vs. an effect of hypoglycemia to directly stimulate glucagon secretion at the level of the islet. Feeding or the cholinergic agonist carbachol increased plasma PP levels in conscious mice (+74 +/- 18 pg/ml vs. fasted mice and +141 +/- 17 pg/ml vs. control, respectively). Neuroglucopenia induced by 2-deoxy-D-glucose or insulin-induced hypoglycemia also increased plasma PP (+79 +/- 18 and +89 +/- 11 pg/ml vs. control, respectively). These increases were abolished by hexamethonium and reduced by atropine methylnitrate (atropine). Hypoglycemia-induced hyperglucagonemia (+1,243 +/- 275 pg/ml) was reduced to 31 +/- 7% of control by atropine (+382 +/- 85 pg/ml), to 48 +/- 9% of control by combined adrenergic blockade (+601 +/- 112 pg/ml), and nearly abolished by atropine plus combined blockade (+143 +/- 41 pg/ml; 11 +/- 3% of control) or hexamethonium (+151 +/- 38 pg/ml; 12 +/- 3% of control). We conclude the following in the mouse. 1) Feeding or cholinergic agonists increase plasma PP. 2) During neuroglucopenia or hypoglycemia, plasma PP is increased via nicotinic and muscarinic mechanisms. 3) The glucagon response to hypoglycemia is predominantly the result of autonomic activation and is mediated by both muscarinic and adrenergic mechanisms.

[1]  B. Dunning,et al.  Corelease of galanin and NE from pancreatic sympathetic nerves during severe hypoglycemia in dogs. , 1992, The American journal of physiology.

[2]  S. Parry,et al.  Autonomic nervous system mediation of the pancreatic polypeptide response to insulin-induced hypoglycemia in conscious rats. , 1992, Endocrinology.

[3]  B. Ahrén,et al.  Contribution of adrenergic nerves and the adrenals to 2-Deoxy-D-glucose-induced insulin and glucagon secretion in the mouse , 1991, International journal of pancreatology : official journal of the International Association of Pancreatology.

[4]  G. Taborsky,et al.  The contribution of the autonomic nervous system to changes of glucagon and insulin secretion during hypoglycemic stress. , 1989, Endocrine reviews.

[5]  M. Passeri,et al.  Effect of muscarinic and nicotinic-cholinergic blockade on the glucagon response to insulin-induced hypoglycemia in normal men. , 1989, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[6]  B. Dunning,et al.  Pancreatic noradrenergic nerves are activated by neuroglucopenia but not by hypotension or hypoxia in the dog. Evidence for stress-specific and regionally selective activation of the sympathetic nervous system. , 1988, The Journal of clinical investigation.

[7]  B. Ahrén,et al.  Inhibition of 2-deoxy-glucose-induced glucagon secretion by muscarinic and alpha-adrenoceptor blockade in the mouse. , 1987, Diabetes research and clinical practice.

[8]  B. Ahrén,et al.  Sympathetic nerve stimulation versus pancreatic norepinephrine infusion in the dog: 1). Effects on basal release of insulin and glucagon. , 1987, Endocrinology.

[9]  J. Halter,et al.  Halothane anesthesia does not suppress sympathetic activation produced by neuroglucopenia. , 1987, The American journal of physiology.

[10]  P. Cryer,et al.  The significance of impaired pancreatic polypeptide and epinephrine responses to hypoglycemia in patients with insulin-dependent diabetes mellitus. , 1987, The Journal of clinical endocrinology and metabolism.

[11]  G. Taborsky,et al.  Halothane is less suppressive than pentobarbital on reflex and neural activation of pancreatic F-cell. , 1986, The American journal of physiology.

[12]  B. Ahrén,et al.  The mechanism of vagal nerve stimulation of glucagon and insulin secretion in the dog. , 1986, Endocrinology.

[13]  B. Ahrén,et al.  Effect and mechanism of vagal nerve stimulation on somatostatin secretion in dogs. , 1986, The American journal of physiology.

[14]  M. Pfeifer,et al.  Pentobarbital suppresses basal and reflexive pancreatic polypeptide release in dogs. , 1985, The American journal of physiology.

[15]  B. Ahrén,et al.  Effects of alpha-adrenoceptor blockade by phentolamine on basal and stimulated insulin secretion in the mouse. , 1985, Acta physiologica Scandinavica.

[16]  D. Patel.  Role of Sympathetic Nervous System in Glucagon Response to Insulin Hypoglycemia in Normal and Diabetic Rats , 1984, Diabetes.

[17]  D. Patel.  Role of parasympathetic nervous system in glucagon response to insulin-induced hypoglycemia in normal and diabetic rats. , 1984, Metabolism: clinical and experimental.

[18]  C. Beglinger,et al.  Pancreatic polypeptide release: role of stimulants of exocrine pancreatic secretion in dogs. , 1984, Gastroenterology.

[19]  K. Alberti,et al.  Effect of epinephrine on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs. , 1984, The American journal of physiology.

[20]  R. Chance,et al.  Pancreatic polypeptide from rat pancreas. , 1984, Endocrinology.

[21]  J. Holst,et al.  Vasoactive intestinal polypeptide (VIP) in the pig pancreas: role of VIPergic nerves in control of fluid and bicarbonate secretion , 1984, Regulatory Peptides.

[22]  T. Adrian,et al.  Neural regulation of pancreatic polypeptide release. , 1983, Surgery.

[23]  B. Ahrén,et al.  Effects of autonomic blockade by methylatropine and optical isomers and propranolol on plasma insulin levels in the basal state and after stimulation. , 1981, Acta physiologica Scandinavica.

[24]  R. Rizza,et al.  Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. Effects of somatostatin and combined alpha- and beta-adrenergic blockade on plasma glucose recovery and glucose flux rates after insulin-induced hypoglycemia. , 1979, The Journal of clinical investigation.

[25]  J. Palmer,et al.  Evaluation of the control of glucagon secretion by the parasympathetic nervous system in man. , 1979, Metabolism: Clinical and Experimental.

[26]  P. Cryer,et al.  Hormonal mechanisms of recovery from insulin-induced hypoglycemia in man. , 1979, The American journal of physiology.

[27]  L. Girardier,et al.  alpha-Sympathetic control of glucose output of mouse liver perfused in situ. , 1979, The American journal of physiology.

[28]  D. Carter,et al.  Effect of atropine and vagotomy on pancreatic polypeptide response to a meal in dogs. , 1978, The American journal of physiology.

[29]  J. Walsh,et al.  Gastric and cephalic stimulation of human pancreatic polypeptide release. , 1978, Gastroenterology.

[30]  J. Holst,et al.  Vagal, cholinergic regulation of pancreatic polypeptide secretion. , 1978, The Journal of clinical investigation.

[31]  T. Adrian,et al.  MECHANISM OF PANCREATIC POLYPEPTIDE RELEASE IN MAN , 1977, The Lancet.

[32]  P. Cryer,et al.  The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man. , 1976, The Journal of clinical investigation.

[33]  J. Rehfeld,et al.  PANCREATIC-POLYPEPTIDE RESPONSE TO FOOD IN DUODENAL-ULCER PATIENTS BEFORE AND AFTER VAGOTOMY , 1976, The Lancet.

[34]  R. Campbell,et al.  Glucagon responses to hypoglycemia in adrenalectomized man. , 1976, Metabolism: clinical and experimental.

[35]  D. Johnson,et al.  Glucagon response to hypoglycemia in sympathectomized man. , 1976, The Journal of clinical investigation.

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

[37]  J. Palmer,et al.  The effect of adrenergic blockade on the glucagon responses to starvation and hypoglycemia in man. , 1974, The Journal of clinical investigation.

[38]  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.

[39]  J. Gerich,et al.  Stimulation of glucagon secretion by epinephrine in man. , 1973, The Journal of clinical endocrinology and metabolism.

[40]  J. Brown.  Atropine, scopolamine and related antimuscarinic drugs , 1990 .

[41]  B. Dunning,et al.  Galanin release during pancreatic nerve stimulation is sufficient to influence islet function. , 1989, The American journal of physiology.

[42]  M. Bruss,et al.  Enzymatic microdetermination of glycogen. , 1978, Analytical biochemistry.