PMID- 11935156
OWN - NLM
STAT- MEDLINE
DCOM- 20020731
LR  - 20181217
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 45
IP  - 2
DP  - 2002 Feb
TI  - Metabotropic glutamate and GABA(B) receptors contribute to the modulation of 
      glucose-stimulated insulin secretion in pancreatic beta cells.
PG  - 242-52
AB  - AIMS/HYPOTHESIS: The neurotransmitters glutamate and gamma-aminobutyric acid 
      (GABA) could participate in the regulation of the endocrine functions of islets 
      of Langerhans. We investigated the role of the metabotropic glutamate (mGluRs) 
      and GABA(B) (GABA(B)Rs) receptors in this process. METHODS: We studied the 
      expression of mGluRs and GABA(B)Rs in rat and human islets of Langerhans and in 
      pancreatic alpha-cell and beta-cell lines using RT-PCR and immunoblot analysis. 
      Effects of mGluR and GABA(B) R agonists on insulin secretion were determined by 
      radioimmunoassays and enzyme-linked immunoadsorbent assays (ELISAs). RESULTS: We 
      detected mGluR3 and mGluR5 (but not mGluR1, 6 and 7) mRNAs in all of the samples 
      examined. Trace amount of mGluR2 was found in MIN6 beta cells; mGluR4 was 
      identified in rat islets; and mGluR8 expression was detected in rat islets, 
      RINm5F and MIN6 cells. GABA(B)R1 a/b and 2 mRNAs were identified in islets of 
      Langerhans and MIN6 cells. The expression of mGluR3, mGluR5, GABA(B)R1 a/b and 
      GABA(B)R2 proteins was confirmed using specific antibodies. Group I (mGluR1/5) 
      and group II (mGluR2/3) specific mGluR agonists increased the release of insulin 
      in the presence of 3 to 10 mmol/l or 3 to 25 mmol/l glucose, respectively, 
      whereas a group III (mGluR4/6-8) specific agonist inhibited insulin release at 
      high (10-25 mmol/l) glucose concentrations. Baclofen, a GABA(B)R agonist, also 
      inhibited the release of insulin but only in the presence of 25 mmol/l glucose. 
      CONCLUSION/INTERPRETATION: These data suggest that mGluRs and GABA(B)Rs play a 
      role in the regulation of the endocrine pancreas with mechanisms probably 
      involving direct activation or inhibition of voltage dependent Ca(2+)-channels, 
      cAMP generation and G-protein-mediated modulation of K(ATP) channels.
FAU - Brice, N L
AU  - Brice NL
AD  - Nuffield Department of Clinical Laboratory Sciences, University of Oxford, UK.
FAU - Varadi, A
AU  - Varadi A
FAU - Ashcroft, S J H
AU  - Ashcroft SJ
FAU - Molnar, E
AU  - Molnar E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (DNA Primers)
RN  - 0 (GRM5 protein, human)
RN  - 0 (Grm5 protein, rat)
RN  - 0 (Insulin)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, GABA-B)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (metabotropic glutamate receptor 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/physiology
MH  - Cell Line
MH  - Cell Membrane/drug effects/physiology
MH  - DNA Primers
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/drug effects/metabolism/*physiology
MH  - Male
MH  - Models, Biological
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Metabotropic Glutamate 5
MH  - Receptors, GABA-B/genetics/*physiology
MH  - Receptors, Metabotropic Glutamate/genetics/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2002/04/06 10:00
MHDA- 2002/08/01 10:01
CRDT- 2002/04/06 10:00
PHST- 2002/04/06 10:00 [pubmed]
PHST- 2002/08/01 10:01 [medline]
PHST- 2002/04/06 10:00 [entrez]
AID - 10.1007/s00125-001-0750-0 [doi]
PST - ppublish
SO  - Diabetologia. 2002 Feb;45(2):242-52. doi: 10.1007/s00125-001-0750-0.