HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weaver, C. D. Articles by Verdoorn, T. A. Search for Related Content PubMed PubMed Citation Articles by Weaver, C. D. Articles by Verdoorn, T. A. Social Bookmarking                      What's this?

Vol. 273, Issue 3, 1647-1653, January 16, 1998

A High Affinity Glutamate/Aspartate Transport System in Pancreatic Islets of Langerhans Modulates Glucose-stimulated Insulin Secretion

C. David Weaver, Vidar Gundersen^¶, and Todd A. Verdoorn

From the  CNS Drug Discovery, Bristol-Meyers Squibb, Wallingford, Connecticut 06492 and the ^¶ Anatomical Institute, University of Oslo, N-0317 Oslo, Norway

To examine the role of glutamatergic signaling in the function of pancreatic islets, we have characterized a high affinity glutamate/aspartate uptake system in this tissue. The islet [³H]glutamate uptake activity was Na⁺-dependent, and it was blocked by L-trans-pyrrolidine-2,4-dicarboxylic acid, a blocker of neuronal and glial glutamate transporters. Islet glutamate transport activity exhibited a V_max of 8.48 ± 1.47 fmol/min/islet (n = 4), which corresponds to 102.2 ± 17.7 pmol/min/mg islet protein. The apparent K_m of islet glutamate transport activity depended on the glucose concentration used in the assay. In the presence of glucose concentrations that do not stimulate insulin secretion (2.8 mM), the apparent K_m was 34.7 ± 7.8 µM (n = 3). However, in high glucose (16.7 mM) the apparent K_m increased to 112.7 ± 16.5 µM (n = 3) with little or no change in V_max. Like most known plasma membrane glutamate transporters, islet glutamate transporters also transported D-aspartate. Anti-D-aspartate immunoreactivity showed that the islet glutamate/aspartate transport activity was localized to the non- cell islet mantle. In perifusion experiments with isolated islets in the absence of exogenous amino acids, L-trans-pyrrolidine-2,4-dicarboxylic acid in the presence of 8.3 mM glucose potentiated insulin secretion 23.3 ± 2.3% (n = 3) compared with 8.3 mM glucose alone. This effect was abolished in the presence of the -amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione. Furthermore, 6-cyano-7-nitroquinoxaline-2,3-dione alone inhibited glucose-stimulated insulin secretion in isolated islets by 15.9 ± 5.9% (n = 3). Taken together these data suggest that a high affinity glutamate transport system exists in pancreatic islets and that this system contributes to a glutamatergic signaling pathway that can modulate glucose-inducible insulin secretion.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. Gromada, I. Franklin, and C. B. Wollheim {alpha}-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains Endocr. Rev., February 1, 2007; 28(1): 84 - 116. [Abstract] [Full Text] [PDF]

				L. Bai, X. Zhang, and F. K. Ghishan Characterization of vesicular glutamate transporter in pancreatic alpha - and beta -cells and its regulation by glucose Am J Physiol Gastrointest Liver Physiol, May 1, 2003; 284(5): G808 - G814. [Abstract] [Full Text] [PDF]

				M. Hayashi, H. Yamada, S. Uehara, R. Morimoto, A. Muroyama, S. Yatsushiro, J. Takeda, A. Yamamoto, and Y. Moriyama Secretory Granule-mediated Co-secretion of L-Glutamate and Glucagon Triggers Glutamatergic Signal Transmission in Islets of Langerhans J. Biol. Chem., January 10, 2003; 278(3): 1966 - 1974. [Abstract] [Full Text] [PDF]

				M. Mourtzakis and T. E. Graham Glutamate ingestion and its effects at rest and during exercise in humans J Appl Physiol, October 1, 2002; 93(4): 1251 - 1259. [Abstract] [Full Text] [PDF]

				Q. Tong, R. Ouedraogo, and A. L. Kirchgessner Localization and function of group III metabotropic glutamate receptors in rat pancreatic islets Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1324 - E1333. [Abstract] [Full Text] [PDF]

				M. Hayashi, M. Otsuka, R. Morimoto, S. Hirota, S. Yatsushiro, J. Takeda, A. Yamamoto, and Y. Moriyama Differentiation-associated Na+-dependent Inorganic Phosphate Cotransporter (DNPI) Is a Vesicular Glutamate Transporter in Endocrine Glutamatergic Systems J. Biol. Chem., November 9, 2001; 276(46): 43400 - 43406. [Abstract] [Full Text] [PDF]

				H. Yamada, M. Otsuka, M. Hayashi, S. Nakatsuka, K. Hamaguchi, A. Yamamoto, and Y. Moriyama Ca2+-Dependent Exocytosis of L-Glutamate by {alpha}TC6, Clonal Mouse Pancreatic {alpha}-Cells Diabetes, May 1, 2001; 50(5): 1012 - 1020. [Abstract] [Full Text]

				A.-C. Rimaniol, S. Haik, M. Martin, R. Le Grand, F. D. Boussin, N. Dereuddre-Bosquet, G. Gras, and D. Dormont Na+-Dependent High-Affinity Glutamate Transport in Macrophages J. Immunol., May 15, 2000; 164(10): 5430 - 5438. [Abstract] [Full Text] [PDF]

				R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis The Glutamate Receptor Ion Channels Pharmacol. Rev., March 1, 1999; 51(1): 7 - 62. [Abstract] [Full Text] [PDF]

				C. D. Weaver, J. G. Partridge, T. L. Yao, J. M. Moates, M. A. Magnuson, and T. A. Verdoorn Activation of Glycine and Glutamate Receptors Increases Intracellular Calcium in Cells Derived from the Endocrine Pancreas Mol. Pharmacol., October 1, 1998; 54(4): 639 - 646. [Abstract] [Full Text]