Early phase insulin infusion and muscarinic blockade in obese and lean subjects.

The effect of early phase insulin on postprandial levels of insulin, C-peptide, glucose, and glucagon was investigated in lean (n = 10) and obese (n = 12) subjects. Subjects underwent four conditions during ingestion of a meal (600 kcal): 1) saline infusion; 2) 10-min insulin infusion simultaneously with meal ingestion (0.24 U bolus, 15 mU. m(-2). min(-1)); 3) atropine infusion (0.4 mg/m(2) bolus, 0.4 mg. m(-2). h for 4 h); 4) insulin and atropine infusion. Blood samples were taken for 3.5 h. Insulin infusion had no effect on postprandial insulin levels in either population but significantly reduced postprandial glucose in the obese subjects (P < 0.05). Obese subjects with elevated postprandial glucose levels in the presence of muscarinic blockade exhibited a decline in glucose with insulin supplementation. Atropine reduced postprandial insulin levels in both groups, with a greater attenuation in the obese (P < 0.01), but postprandial glucose levels were also significantly reduced, suggesting that atropine inhibited gastric emptying. Thus the effects of muscarinic blockade on postprandial insulin levels cannot be evaluated. These data suggest that insulin supplementation during the preabsorptive time period may contribute to glucoregulation in the obese population.

[1]  R. Adkins,et al.  Role of hepatic nerves in response of liver to intraportal glucose delivery in dogs. , 1992, The American journal of physiology.

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

[3]  D. Bruce,et al.  Mind over metabolism: The cephalic phase in relation to non-insulin-dependent diabetes and obesity , 1989, Biological Psychology.

[4]  A. Cherrington,et al.  Comparison of the time courses of insulin and the portal signal on hepatic glucose and glycogen metabolism in the conscious dog. , 1996, The Journal of clinical investigation.

[5]  J. Peters,et al.  Cholinergic blockade with pirenzepine induces dose‐related reduction in glucose and insulin responses to a mixed meal in normal subjects and non‐insulin dependent diabetics , 1991, Clinical endocrinology.

[6]  B. Jeanrenaud,et al.  Hyperinsulinemia of preobese and obese fa/fa rats is partly vagus nerve mediated. , 1983, The American journal of physiology.

[7]  M. Feinglos,et al.  Muscarinic Stimulation and Antagonism and Glucoregulation in Nondiabetic and Obese Hyperglycemic Mice , 1989, Diabetes.

[8]  L. Campfield,et al.  Neural control of insulin secretion: interaction of norepinephrine and acetylcholine. , 1983, The American journal of physiology.

[9]  J. Felber,et al.  Effects of cholinergic stimulation and antagonism on plasma insulin concentration in lean and obese human subjects. , 1986, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[10]  K. Nakao,et al.  Effects of stimulation of the vagus nerve on insulin secretion. , 1967, Endocrinology.

[11]  M. Bondi,et al.  Cholinergic enhancement by pyridostigmine increases the insulin response to glucose load in obese patients but not in normal subjects , 1997, International Journal of Obesity.

[12]  A. Steffens Influence of the oral cavity on insulin release in the rat. , 1976, The American journal of physiology.

[13]  W. G. Johnson,et al.  Influence of external and covert food stimuli on insulin secretion in obese and normal persons. , 1983, Behavioral neuroscience.

[14]  E. Jéquier,et al.  Effects of muscarinic blockade on insulin secretion and on glucose‐induced thermogenesis in lean and obese human subjects , 1991, European journal of clinical investigation.

[15]  J. Holst,et al.  Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans , 1997 .

[16]  G. Reaven,et al.  Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system. , 1996, The New England journal of medicine.

[17]  H. Rasmussen,et al.  Cholinergic agonists prime the beta-cell to glucose stimulation. , 1989, Endocrinology.

[18]  P. Cryer,et al.  Evidence against the hypothesis that hyperinsulinemia increases sympathetic nervous system activity in man. , 1992, Metabolism: clinical and experimental.

[19]  E. Kraegen,et al.  Physiological Importance of Deficiency in Early Prandial Insulin Secretion in Non-Insulin-Dependent Diabetes , 1988, Diabetes.

[20]  J. Callés-Escandon,et al.  Loss of Early Phase of Insulin Release in Humans Impairs Glucose Tolerance and Blunts Thermic Effect of Glucose , 1987, Diabetes.

[21]  H. Berthoud,et al.  Importance of cholinergic innervation of the pancreas for glucose tolerance in the rat. , 1981, The American journal of physiology.

[22]  R. Bergman,et al.  Free Fatty Acid as a Link in the Regulation of Hepatic Glucose Output by Peripheral Insulin , 1995, Diabetes.

[23]  J. Peters,et al.  Acute cholinergic blockade with low dose pirenzepine reduces the insulin and glucose responses to a mixed meal in obese women with the polycystic ovary syndrome , 1994, Clinical endocrinology.

[24]  J. Stern,et al.  Tonic sympathetic nervous system inhibition of insulin secretion is diminished in obese Zucker rats. , 1993, Obesity research.

[25]  R. Mattes,et al.  Cephalic-phase insulin in obese and normal-weight men: relation to postprandial insulin. , 1993, Metabolism: clinical and experimental.

[26]  R. DeFronzo,et al.  Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C. Beglinger,et al.  Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade , 1995, European journal of clinical investigation.

[28]  W. W. Lautt,et al.  Induction of insulin resistance by cholinergic blockade with atropine in the cat. , 1995, Journal of autonomic pharmacology.

[29]  P. Guth,et al.  Vagal nerve stimulation causes noncholinergic dilatation of gastric arterioles. , 1986, The American journal of physiology.

[30]  R. Bergman,et al.  Direct enhancement of insulin secretion by vagal stimulation of the isolated pancreas. , 1973, The American journal of physiology.

[31]  T. Powley,et al.  The ventromedial hypothalamic syndrome, satiety, and a cephalic phase hypothesis. , 1977, Psychological review.

[32]  E. Kraegen,et al.  Timing of Insulin Delivery with Meals , 1981, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[33]  H. Najafi,et al.  Acetylcholine stimulates glucose metabolism by pancreatic islets. , 1986, Life sciences.

[34]  J. R. Henderson,et al.  The effect of atropine on the insulin release caused by oral and intravenous glucose in human subjects. , 1976, Acta endocrinologica.

[35]  K Engelman,et al.  Cephalic phase insulin release in normal weight males: verification and reliability. , 1991, The American journal of physiology.

[36]  L. Storlien The role of the ventromedial hypothalamic area in periprandial glucoregulation. , 1985, Life sciences.

[37]  D. McTigue,et al.  Vagal control of digestion: Modulation by central neural and peripheral endocrine factors , 1996, Neuroscience & Biobehavioral Reviews.

[38]  L. Christin,et al.  Thermic effect of food: possible implication of parasympathetic nervous system. , 1987, The American journal of physiology.

[39]  S. Grottoli,et al.  Effects of cholinergic blockade by pirenzepine on insulin and glucose response to oral and intravenous glucose and to arginine load in obesity , 1997, Journal of endocrinological investigation.

[40]  T. Shimazu Glycogen Synthetase Activity in Liver: Regulation by the Autonomic Nerves , 1967, Science.

[41]  M. Classen,et al.  Circulating amino acids and pancreatic endocrine function after ingestion of a protein-rich meal in obese subjects. , 1989, The Journal of clinical endocrinology and metabolism.

[42]  K. Teff,et al.  Oral sensory stimulation improves glucose tolerance in humans: effects on insulin, C-peptide, and glucagon. , 1996, The American journal of physiology.

[43]  B. Levin,et al.  Oral sensory stimulation in men: effects on insulin, C-peptide, and catecholamines. , 1993, The American journal of physiology.

[44]  B. Jeanrenaud,et al.  Involvement of the cholinergic system in insulin and glucagon oversecretion of genetic preobesity. , 1985, Endocrinology.

[45]  L. Sjöström,et al.  Peripheral insulin in response to the sight and smell of food. , 1980, Metabolism: clinical and experimental.

[46]  J. Holst,et al.  Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. , 1997, The Journal of clinical endocrinology and metabolism.

[47]  R. Bergman,et al.  Indirect effect of insulin to suppress endogenous glucose production is dominant, even with hyperglucagonemia. , 1997, The Journal of clinical investigation.

[48]  S. Bloom,et al.  Vagal control of glucagon release in man. , 1974, Lancet.

[49]  R. Bergman,et al.  Novel Glucosensor for Hypoglycemic Detection Localized to the Portal Vein , 1997, Diabetes.

[50]  J. Proietto,et al.  Role of the Oropharynx in Regulation of Glycemia , 1987, Diabetes.

[51]  M. Harada,et al.  Gastric blood flow responses to autonomic nerve stimulation and related pharmacological studies in rats , 1983, The Journal of pharmacy and pharmacology.

[52]  A. Cherrington,et al.  Importance of the route of intravenous glucose delivery to hepatic glucose balance in the conscious dog. , 1987, The Journal of clinical investigation.

[53]  A. Alavi,et al.  Muscarinic blockade inhibits gastric emptying of mixed-nutrient meal: effects of weight and gender. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[54]  P. Cryer,et al.  Direct muscarinic cholinergic inhibition of hepatic glucose production in humans. , 1988, The Journal of clinical investigation.