Skip to main content
Log in

Effect of Motilin on Endogenous Release of Insulin in Conscious Dogs in the Fed State

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The aim was to investigate the insulin-releasing activity of motilin during and after feeding. A single intravenous bolus injection of motilin (0.01–0.3 μg/kg) dose-dependently stimulated endogenous release of insulin in the postprandial state. The insulin-releasing activity of motilin in the fed state was completely abolished by pretreatment with atropine or hexamethonium and was partly inhibited by ondansetron. Truncal vagotomy also greatly suppressed the motilin-induced insulin release. While phentolamine significantly enhanced insulin release in response to motilin, propranolol significantly inhibited this response in both states. The motilin-induced insulin release in the fed states was not accompanied by any changes in glucose concentrations. In conclusion, while the physiological significance remains unclear, these results indicate that physiological doses of motilin stimulate endogenous release of insulin via a vagally cholinergic muscarinic pathway, and that adrenergic and 5-hydroxytryptamine3 receptors are also involved in this response, in the dog.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Unger RH, Eisentraut AM: Entero-insular axis. Arch Intern Med 123:261-266, 1969

    Google Scholar 

  2. Pederson RA, Browen JC: Interaction of gastric inhibitory polypeptide, glucose, and arginine on insulin and glucagon secretion from the perfused rat pancreas. Endocrinology 103:610-615, 1978

    Google Scholar 

  3. Suzuki H, Mochiki E, Haga N, Satoh M, Mizumoto A, Itoh Z: Motilin controls interdigestive cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs. Am J Physiol 274:G87-G95, 1998

    Google Scholar 

  4. Brown JC, Cook MA, Dryburgh JR: Motilin, a gastric motor activity stimulating polypeptide: The complete amino acid sequence. Can J Biochem 51:533-537, 1973

    Google Scholar 

  5. Buchan AM, Polak JM, Capella C, Solcia E, Pearse AG: Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) in man. Histochemistry 56:37-44, 1978

    Google Scholar 

  6. Mori K, Seino Y, Itoh Z, Yanaihara N, Imura H: Motilin release by intravenous infusion of nutrients and somatostatin in conscious dogs. Reg Pept 1:265-270, 1981

    Google Scholar 

  7. Itoh Z, Takeuchi S, Aizawa I, Mori K, Taminato T, Seino Y, Imura H, Yanaihara N: Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs. Am J Dig Dis 23:929-935, 1978

    Google Scholar 

  8. Lee KY, Chey Wy, Tai HH, Yajima H: Radioimmunoassay of motilin: validation and studies on the relationship between plasma motilin and interdigestive myoelectric activity of the duodenum of dog. Am J Dig Dis 23:789-795, 1978

    Google Scholar 

  9. Itoh Z, Honda R, Hiwatashi K, Takeuchi S, Aizawa I, Takayanagi R, Couch EF: Motilin-induced mechanical activity in the canine alimentary tract. Scand J Gastroent 11 (Suppl 39):93-110, 1976

    Google Scholar 

  10. Lee KY, Chang TM, Chey WY: Effect of rabbit antimotilin serum on myoelectric activity and plasma motilin concentration in fasting dog. Am J Physiol 245:G547-G553, 1983

    Google Scholar 

  11. Itoh Z, Honda R, Takeuchi S, Aizawa I, Takayanagi R: An extraluminal force transducer for recording contractile activity of the gastrointestinal smooth muscle: Its construction and implantation. Gastroenterol Jpn 12:275-283, 1977

    Google Scholar 

  12. Shiba Y, Mizumoto A, Satoh M, Inui A, Itoh Z, Omura S: Effect of nonpeptide motilin agonist EM523 on release of gut and pancreatic hormones in conscious dogs. Gastroenterology 110:241-250, 1996

    Google Scholar 

  13. Flore M, Mitchell T, Doan R, Nelson R, Winter G, Grandone C, Zeng K, Harden R, Smith J, Harris K: The abbott IMxTM automated benchtop immunochemistry analyzer system. Clin Chem 34:1726-1732, 1988

    Google Scholar 

  14. Mochiki E, Satoh M, Tamura T, Haga N, Suzuki H, Mizumoto A, Sakai T, Itoh Z: Exogenous motilin stimulates endogenous release of motilin through cholinergic muscarinic pathways in the dog. Gastroenterology 111:1456-1464, 1996

    Google Scholar 

  15. Itoh Z, Takeuchi S, Aizawa I, Takayanagi R: Characteristic motor activity of the gastrointestinal tract in fasted conscious dogs measured by implanted force transducers. Am J Dig Dis 23:229-238, 1978

    Google Scholar 

  16. Szurszewski JH: A migrating electric complex of the canine small intestine. Am J Physiol 217:1757-1763, 1969

    Google Scholar 

  17. Perley MJ, Kipnis DM: Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 46:1954-1962, 1967

    Google Scholar 

  18. McIntyre N, Holdsworth CD, Turner DS: New interpretation of oral glucose tolerance. Lancet 2:20-21, 1964

    Google Scholar 

  19. Elrick H, Stimmer L, Hlad CJ, Arai Y: Plasma insulin response to oral and intravenous glucose tolerance. J Clin Endocrinol 24:1076-1082, 1964

    Google Scholar 

  20. Goldberg NJ, Wingert TD, Levin SR, Adachi RI: Augmentation of insulin secretion by a non-nutrient drink. Gastroenterology 78:1458-1462, 1980

    Google Scholar 

  21. Creutzfeldt W: The incretin concept today. Diabetologia 16:75-85, 1979

    Google Scholar 

  22. Rabinovitch A, Dupre J: Effects of the gastric inhibitory polypeptide present in impure pancreozymin-cholecystokinin on plasma insulin and glucagon in the rat. Endocrinology 94:1139-1144, 1974

    Google Scholar 

  23. Dupre J, Ross SA, Watson D, Brown JC: Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrionl Metab 37:826-828, 1973

    Google Scholar 

  24. Sarson DL, Wood SM, Kansal PC, Bloom SR: Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology? Diabetes 33:389-393, 1984

    Google Scholar 

  25. Ebert R, Illmer K, Creutzfeldt W: Release of gastric inhibitory polypeptide (GIP) by intraduodenal acidification in rats and humans and abolishment of the incretin effect of acid by GIP-antiserum in rats. Gastroenterology 76:515-523, 1979

    Google Scholar 

  26. Schwartz TW, Holst JJ, Fahrenkrug J, Jensen SL, Nielsen OV, Rehfeld JF, Schaffalitzky de Muckadell OB, Stadil F: Vagal, cholinergic regulation of pancreatic polypeptide secretion. J Clin Invest 61:781-789, 1978

    Google Scholar 

  27. Frohman LA, Ezdinli EZ, Javid R: Effect of vagotomy and vagal stimulation on insulin secretion. Diabetes 16:443-448, 1967

    Google Scholar 

  28. Schwartz TW: Pancreatic polypeptide: A hormone under vagal control. Gastroenterology 85:1411-1425, 1983

    Google Scholar 

  29. Ahren B, Taborsky GJ: The mechanism of vagal nerve stimulation of glucagon and insulin secretion in the dog. Endocrinology 118:1551-1557, 1986

    Google Scholar 

  30. Berthoud H-R, Fox WA, Powley TL: Localization of vagal preganglionics that stimulate insulin and glucagon secretion. Am J Physiol 258:R160-R168, 1990

    Google Scholar 

  31. Stagner JI, Samols E: Role of intrapancreatic ganglia in regulation of periodic insular secretions. Am J Physiol 248:E522-E530, 1985

    Google Scholar 

  32. Larsson LI, Rehfeld JF: Peptidergic and adrenergic innervation of pancreatic ganglia. Scand J Gastroenterol 14:433-437, 1979

    Google Scholar 

  33. Miller RE: Pancreatic neuroendocrinology: Peripheral neural mechanisms in the regulation of the islets of Langerhans. Endocr Rev 2:471-494, 1981

    Google Scholar 

  34. Malaisse W, Malaisse-Lagae F, Wright PH, Ashmore J: Effects of adrenergic and cholinergic agents upon insulin secretion in vitro. Endocrinology 80:975-978, 1967

    Google Scholar 

  35. Kaneto A, Sato H, Kaneko T, Yanaihara C, Yanaihara N, Kosaka K: Stimulation of somatostatin, pancreatic polypeptide, glucagon and insulin secretion by acetylcholine infused intrapancreatically in dogs. Biomed Res 2:57-66, 1981

    Google Scholar 

  36. Mochiki E, Inui A, Satoh M, Mizumoto A, Itoh Z: Motilin is a biosignal controlling the cyclic release of pancreatic polypeptide via the vagus in fasted dogs. Am J Physiol 272:G224-G232, 1997

    Google Scholar 

  37. Iversen J: Adrenergic receptors and the secretion of glucagon and insulin from the isolated, perfused canine pancreas. J Clin Invest 52:2102-2116, 1973

    Google Scholar 

  38. Itoh Z, Takahashi I: Periodic contractions of the canine gallbladder during the interdigestive state. Am J Physiol 240:G183-G189, 1981

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suzuki, H., Kuwano, H., Mochiki, E. et al. Effect of Motilin on Endogenous Release of Insulin in Conscious Dogs in the Fed State. Dig Dis Sci 48, 2263–2270 (2003). https://doi.org/10.1023/B:DDAS.0000007861.91075.b3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:DDAS.0000007861.91075.b3

Navigation