Localization and function of group III metabotropic glutamate receptors in rat pancreatic islets

• Published in: American journal of physiology: endocrinology and metabolism Vol. 282; no. 6; pp. E1324 - E1333
• Main Authors: Tong, Qingchun, Ouedraogo, Raogo, Kirchgessner, Annette L
• Format: Journal Article
• Language: English
• Published: United States 01.06.2002
• Subjects: Animals; Benzoates - pharmacology; Cell Membrane - chemistry; Colforsin - pharmacology; Cyclic AMP - metabolism; Cytoplasmic Granules - chemistry; DNA Primers; Excitatory Amino Acid Antagonists - pharmacology; Female; Gene Expression; Glucagon - secretion; Glutamic Acid - analysis; Glycine - analogs & derivatives; Glycine - pharmacology; Islets of Langerhans - chemistry; Islets of Langerhans - physiology; Microscopy, Immunoelectron; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - analysis; Receptors, Metabotropic Glutamate - genetics; Receptors, Metabotropic Glutamate - physiology; Reverse Transcriptase Polymerase Chain Reaction; Synaptophysin - analysis; Tissue Distribution
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00460.2001

Program of Neural and Behavioral Sciences, Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203 Pancreatic islets contain ionotropic glutamate receptors that can modulate hormone secretion. The purpose of this study was to determine whether islets express functional group III metabotropic glutamate (mGlu) receptors. RT-PCR analysis showed that rat islets express the mGlu8 receptor subtype. mGlu8 receptor immunoreactivity was primarily displayed by glucagon-secreting -cells and intrapancreatic neurons. By demonstrating the immunoreactivities of both glutamate and the vesicular glutamate transporter 2 (VGLUT2) in these cells, we established that -cells express a glutamatergic phenotype. VGLUT2 was concentrated in the secretory granules of islet cells, suggesting that glutamate might play a role in the regulation of glucagon processing. The expression of mGlu8 by glutamatergic cells also suggests that mGlu8 may function as an autoreceptor to regulate glutamate release. Pancreatic group III mGlu receptors are functional because mGlu8 receptor agonists inhibited glucagon release and forskolin-induced accumulation of cAMP in isolated islets, and (R,S)-cyclopropyl-4-phosphonophenylglycine, a group III mGlu receptor antagonist, reduced these effects. Because excess glucagon secretion causes postprandial hyperglycemia in patients with type 2 diabetes, group III mGlu receptor agonists could be of value in the treatment of these patients. glutamate; glucagon; vesicular glutamate transporter 2; (R,S)-4-phosphonophenylglycine; (S)-3,4-dicarboxyphenylglycine; (R,S)-cyclopropyl-4-phosphonophenylglycine; cyclic adenosine monophosphate