RGD Reference Report - Type VIII adenylyl cyclase in rat beta cells: coincidence signal detector/generator for glucose and GLP-1. - Rat Genome Database

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Type VIII adenylyl cyclase in rat beta cells: coincidence signal detector/generator for glucose and GLP-1.

Authors: Delmeire, D  Flamez, D  Hinke, SA  Cali, JJ  Pipeleers, D  Schuit, F 
Citation: Delmeire D, etal., Diabetologia. 2003 Oct;46(10):1383-93. Epub 2003 Sep 17.
RGD ID: 2312682
Pubmed: PMID:13680124   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-003-1203-8   (Journal Full-text)

AIMS/HYPOTHESIS: The secretory function of pancreatic beta cells is synergistically stimulated by two signalling pathways which mediate the effects of nutrients and hormones such as glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or glucagon. These hormones are known to activate adenylyl cyclase in beta cells. We examined the type of adenylyl cyclase that is associated with this synergistic interaction. METHODS: Insulin release, cAMP production, adenylyl cyclase activity, mRNA and protein expression were measured in fluorescence-activated cell sorter-purified rat beta cells and in the rat beta-cell lines RINm5F, INS-1 832/13 and INS-1 832/2. RESULTS: In primary beta cells, glucagon and GLP-1 synergistically potentiate the stimulatory effect of 20 mmol/l glucose on insulin release and cAMP production. Both effects are abrogated in the presence of the L-type Ca(2+)-channel blocker verapamil. The cAMP-producing activity of adenylyl cyclase in membranes from RINm5F cells is synergistically increased by Ca(2+)-calmodulin and recombinant GTP(gamma)S-activated G(s alpha)-protein subunits. This type of regulation is characteristic for type I and type VIII AC isoforms. Consistent with this functional data, AC mRNA analysis shows abundant expression of type VI AC, four splice variants of type VIII AC and low expression level of type I AC in beta cells. Type VIII AC expression at the protein level was observed using immunoblots of RINm5F cell extracts. CONCLUSION/INTERPRETATION: This study identifies type VIII AC in insulin-secreting cells as one of the potential molecular targets for synergism between GLP-1 receptor mediated and glucose-mediated signalling.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adcy8Ratcellular response to forskolin involved_inIDA PMID:13680124UniProt 
Adcy8Ratglucose mediated signaling pathway involved_inIDA PMID:13680124UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adcy8Ratplasma membrane located_inIDA PMID:13680124UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GnasRatadenylate cyclase activator activity enablesIDA PMID:13680124UniProt 
Adcy8Ratcalcium- and calmodulin-responsive adenylate cyclase activity enablesIDA PMID:13680124UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Adcy8  (adenylate cyclase 8)
Gnas  (GNAS complex locus)


Additional Information