QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.018390v1 69/4/1234    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Storto, M. Articles by Nicoletti, F. Search for Related Content PubMed PubMed Citation Articles by Storto, M. Articles by Nicoletti, F.

Original Article

Insulin Secretion Is Controlled by mGlu5 Metabotropic Glutamate Receptors

I.N.M. Neuromed, Pozzilli, Italy (M.S., L.C., G.B., G.M., R.G., B.R., A.D.M., V.B., F.N.); Departments of Experimental Medicine (R.G.), and Human Physiology and Pharmacology (V.B., F.N.), University of Rome "La Sapienza", Rome, Italy; Department of Biochemistry and Henry Wellcome Laboratories for Integrated Cell Signalling, University of Bristol, Bristol, United Kingdom (K.J.M., G.A.R.); and Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy (M.P.V.)

Abstract

Recent evidence suggests that metabotropic glutamate (mGlu) receptors are involved in the regulation of hormone secretion in the endocrine pancreas. We report here that endogenous activation of mGlu5 receptors is required for an optimal insulin response to glucose both in clonal -cells and in mice. In clonal -cells, mGlu5 receptors were expressed at the cell surface and were also found in purified insulin-containing granules. These cells did not respond to a battery of mGlu5 receptor agonists that act extracellularly, but instead responded to a cell-permeant analog of glutamate with an increase in [Ca²⁺]_i and insulin secretion. Both effects were largely attenuated by the mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP). MPEP and its structural analog, (E)-2-methyl-6-styryl-pyridine (SIB-1893), reduced the increase in [Ca²⁺]_i and insulin secretion induced by glucose in clonal -cells, whereas a mGlu1 receptor antagonist was inactive. mGlu5 knockout mice showed a defective insulin response at all times after a glucose pulse (1.5 g/kg, i.p.), whereas wild-type mice treated with MPEP (10 mg/kg, i.p.) showed a selective impairment in the late phase of insulin secretion in response to glucose challenge. Mice injected with MPEP or lacking mGlu5 receptors also showed a blunted glucagon response to an insulin challenge. We conclude that insulin secretion is under the control of mGlu5 receptors both in clonal -cells and in vivo. Drugs that modulate the function of mGlu5 receptors might affect glucose homeostasis by altering the secretion of pancreatic hormones.

Address correspondence to: Dr. Ferdinando Nicoletti, Department of Human Physiology and Pharmacology, University of Rome "La Sapienza", Piazzale Aldo Moro, 5, 00185 Rome, Italy. E-mail: ferdinandonicoletti{at}hotmail.com

This article has been cited by other articles:

				A. Raffo, K. Hancock, T. Polito, Y. Xie, G. Andan, P. Witkowski, M. Hardy, P. Barba, C. Ferrara, A. Maffei, et al. Role of vesicular monoamine transporter type 2 in rodent insulin secretion and glucose metabolism revealed by its specific antagonist tetrabenazine J. Endocrinol., July 1, 2008; 198(1): 41 - 49. [Abstract] [Full Text] [PDF]

				B. G. Forde and P. J. Lea Glutamate in plants: metabolism, regulation, and signalling J. Exp. Bot., July 1, 2007; 58(9): 2339 - 2358. [Abstract] [Full Text] [PDF]