| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
-Aminobutyric Acid on Hormone Release by the Mouse and Rat Endocrine Pancreas*
Unité de Diabétologie et Nutrition, University of Louvain, Faculty of Medicine(P.G., J.C.H.) B-1200 Brussels
Laboratoire de Biobgie Cellulaire, University of Louvain, Faculty of Sciences (C.R.) B-1348 Louvain-la-Neuve, Belgium
Laboratoire de Pharmacologie, URA 599 of the CNRS, Institute of Biology, Faculty of Medicine (G.B., M.M.L.M.) F-34060 Montpellier, France
Address all correspondence and requests for reprints to: Dr. J. C. Henquin, Unite de Diabetologie et Nutrition, U.C.L. 54.74, Avenue Hippocrate 54, B-1200 Brussels, Belgium.
Abstract
The present study was aimed at localizing 
-aminobutyric acid (GABA) and its enzyme of synthesis, glutamic acid decarboxylase (GAD), in the mouse pancreas by immunocytochemical methods. The influence of GABA on hormone release was also studied with normal mouse and rat islets and the isolated perfused rat pancreas. Particular attention was paid to glucagon release to test a recent hypothesis suggesting that GABA mediates the still unexplained glucose-induced inhibition of glucagon release. GABA and GAD were identified only in islet cells and never in the exocrine tissue. Exogenous GABA, baclofen (agonist of GABAB receptors), muscimol (agonist of GABAA receptors), or bicuculline (antagonist of GABAA receptors) did not affect insulin and somatostatin release by isolated mouse or rat islets. GABA was also without effect on glucose-induced electrical activity in mouse B-cells. Glucagon secretion by mouse islets was only slightly inhibited (–20%) by GABA. Since muscimol had a similar effect, and baclofen was ineffective, the inhibition by GABA probably involves GABAA receptor activation. Bicuculline, however, did not antagonize the inhibitory effects of GABA and muscimol, probably because the antagonist alone also decreased glucagon secretion. In contrast to GABA, low (3 mM) and high (20 mMJ concentrations of glucose strongly inhibited (–50–65%) glucagon release; this inhibition was not prevented by bicuculline. Similar results were obtained with the perfused rat pancreas; muscimol slightly inhibited glucagon release under various conditions, and bicuculline did not reverse the strong inhibition produced by 16.7 mM glucose. In conclusion, GABA does not affect insulin and somatostatin secretion, but inhibits A-cells, probably by acting on GABAA receptors. It is unlikely, however, that this small inhibitory effect can account for the inhibition of glucagon release produced by glucose. (Endocrinology 129: 2521–2529,1991)
Footnotes
* This work was supported in part by Grant 3.4607.90 from the FRSM, Brussels, and Grant SPPS-AC 89/95-135 from the Ministry of Scientific Policy, Brussels.
Charge de Recherches of the UCL, Brussels, Belgium.
Directeur de Recherches of the FNRS, Brussels, Belgium.
Received April 30, 1991.
This article has been cited by other articles:
 |
|
 |
|
  S. Z. Young and A. Bordey GABA's Control of Stem and Cancer Cell Proliferation in Adult Neural and Peripheral Niches Physiology, June 1, 2009; 24(3): 171 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Rutter Regulating Glucagon Secretion: Somatostatin in the Spotlight Diabetes, February 1, 2009; 58(2): 299 - 301. [Full Text] [PDF]
|
|
|
|
|
|
N. Quoix, R. Cheng-Xue, L. Mattart, Z. Zeinoun, Y. Guiot, M. C. Beauvois, J.-C. Henquin, and P. Gilon Glucose and Pharmacological Modulators of ATP-Sensitive K+ Channels Control [Ca2+]c by Different Mechanisms in Isolated Mouse {alpha}-Cells Diabetes, February 1, 2009; 58(2): 412 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bansal and Q. Wang Insulin as a physiological modulator of glucagon secretion Am J Physiol Endocrinol Metab, October 1, 2008; 295(4): E751 - E761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Bonaventura, P. N. Catalano, A. Chamson-Reig, E. Arany, D. Hill, B. Bettler, F. Saravia, C. Libertun, and V. A. Lux-Lantos GABAB receptors and glucose homeostasis: evaluation in GABAB receptor knockout mice Am J Physiol Endocrinol Metab, January 1, 2008; 294(1): E157 - E167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, R. Mao, M. Van De Casteele, D. Pipeleers, and Z. Ling Glucagon-like peptide-1 stimulates GABA formation by pancreatic beta-cells at the level of glutamate decarboxylase Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1201 - E1206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. J. Bailey, M. A. Ravier, and G. A. Rutter Glucose-Dependent Regulation of {gamma}-Aminobutyric Acid (GABAA) Receptor Expression in Mouse Pancreatic Islet {alpha}-Cells Diabetes, February 1, 2007; 56(2): 320 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, K. Kerckhofs, M. Van de Casteele, I. Smolders, D. Pipeleers, and Z. Ling Glucose inhibits GABA release by pancreatic beta-cells through an increase in GABA shunt activity Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E494 - E499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Braun, A. Wendt, K. Buschard, A. Salehi, S. Sewing, J. Gromada, and P. Rorsman GABAB receptor activation inhibits exocytosis in rat pancreatic {beta}-cells by G-protein-dependent activation of calcineurin J. Physiol., September 1, 2004; 559(2): 397 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Metzeler, A. Agoston, and M. Gratzl An Intrinsic {gamma}-Aminobutyric Acid (GABA)ergic System in the Adrenal Cortex: Findings from Human and Rat Adrenal Glands and the NCI-H295R Cell Line Endocrinology, May 1, 2004; 145(5): 2402 - 2411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Uehara, A. Muroyama, N. Echigo, R. Morimoto, M. Otsuka, S. Yatsushiro, and Y. Moriyama Metabotropic Glutamate Receptor Type 4 Is Involved in Autoinhibitory Cascade for Glucagon Secretion by {alpha}-Cells of Islet of Langerhans Diabetes, April 1, 2004; 53(4): 998 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wendt, B. Birnir, K. Buschard, J. Gromada, A. Salehi, S. Sewing, P. Rorsman, and M. Braun Glucose Inhibition of Glucagon Secretion From Rat {alpha}-Cells Is Mediated by GABA Released From Neighboring {beta}-Cells Diabetes, April 1, 2004; 53(4): 1038 - 1045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. K. Franklin and C. B. Wollheim GABA in the Endocrine Pancreas: Its Putative Role as an Islet Cell Paracrine-signalling Molecule J. Gen. Physiol., February 23, 2004; 123(3): 185 - 190. [Full Text] [PDF]
|
|
|
|
|
|
M. Hayashi, M. Otsuka, R. Morimoto, A. Muroyama, S. Uehara, A. Yamamoto, and Y. Moriyama Vesicular Inhibitory Amino Acid Transporter Is Present in Glucagon-Containing Secretory Granules in {alpha}TC6 Cells, Mouse Clonal {alpha}-Cells, and {alpha}-Cells of Islets of Langerhans Diabetes, August 1, 2003; 52(8): 2066 - 2074. [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]
|
|
|
|
|
|
J. Bustamante, M. V. T. Lobo, F. J. Alonso, N.-T. A. Mukala, E. Gine, J. M. Solis, J. Tamarit-Rodriguez, and R. Martin Del Rio An osmotic-sensitive taurine pool is localized in rat pancreatic islet cells containing glucagon and somatostatin Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1275 - E1285. [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]
|
|
|
|
 |
|
 H. S. Park and H. J. Park Effects of gamma -aminobutyric acid on secretagogue-induced exocrine secretion of isolated, perfused rat pancreas Am J Physiol Gastrointest Liver Physiol, October 1, 2000; 279(4): G677 - G682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Shi, J. Kanaani, V. Menard-Rose, Y. H. Ma, P.-Y. Chang, D. Hanahan, A. Tobin, G. Grodsky, and S. Baekkeskov Increased expression of GAD65 and GABA in pancreatic beta -cells impairs first-phase insulin secretion Am J Physiol Endocrinol Metab, September 1, 2000; 279(3): E684 - E694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Takahashi, T. Kadowaki, Y. Yazaki, Y. Miyashita, and H. Kasai Multiple Exocytotic Pathways in Pancreatic {beta} Cells J. Cell Biol., July 14, 1997; 138(1): 55 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rubi, H. Ishihara, F. G. Hegardt, C. B. Wollheim, and P. Maechler GAD65-mediated Glutamate Decarboxylation Reduces Glucose-stimulated Insulin Secretion in Pancreatic Beta Cells J. Biol. Chem., September 21, 2001; 276(39): 36391 - 36396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Winnock, Z. Ling, R. De Proft, S. Dejonghe, F. Schuit, F. Gorus, and D. Pipeleers Correlation between GABA release from rat islet beta -cells and their metabolic state Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E937 - E942. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
