RGD Reference Report - Protein inhibitor of neuronal nitric oxide synthase (PIN) is a new regulator of glucose-induced insulin secretion. - Rat Genome Database

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Protein inhibitor of neuronal nitric oxide synthase (PIN) is a new regulator of glucose-induced insulin secretion.

Authors: Lajoix, AD  Badiou, S  Peraldi-Roux, S  Chardes, T  Dietz, S  Aknin, C  Tribillac, F  Petit, P  Gross, R 
Citation: Lajoix AD, etal., Diabetes. 2006 Dec;55(12):3279-88.
RGD ID: 1642149
Pubmed: PMID:17130471   (View Abstract at PubMed)
DOI: DOI:10.2337/db06-0257   (Journal Full-text)

We previously showed that pancreatic beta-cells express neuronal nitric oxide synthase (nNOS) that controls insulin secretion through two catalytic activities: nitric oxide (NO) production and cytochrome c reductase activity. We now provide evidence that the endogenous protein inhibitor of nNOS (PIN) is expressed in rat pancreatic islets and INS-1 cells. Double-immunofluorescence studies showed a colocalization of PIN with both nNOS and myosin Va in insulin-secreting beta-cells. Electron microscopy studies confirmed that PIN is mainly associated with insulin secretory granules and colocated with nNOS in the latter. In addition, PIN overexpression in INS-1 cells enhanced glucose-induced insulin secretion, which is only partly reversed by addition of an NO donor, sodium nitroprusside (SNP), and unaffected by the inhibitor of cytochrome c reductase activity, miconazole. In contrast, the pharmacological inhibitor of nNOS, Nomega-nitro-l-arginine methyl ester, amplified glucose-induced insulin secretion, an effect insensitive to SNP but completely normalized by the addition of miconazole. Thus, PIN insulinotropic effect could be related to its colocalization with the actin-based molecular motor myosin Va and as such be implicated in the physiological regulation of glucose-induced insulin secretion at the level of the exocytotic machinery.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nos1Ratnegative regulation of insulin secretion  IMP  RGD 
Dynll1Ratpositive regulation of insulin secretion involved in cellular response to glucose stimulus  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Dynll1Ratsecretory granule  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Dynll1Ratidentical protein binding  IPIDynll1 (Rattus norvegicus)homodimerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Dynll1  (dynein light chain LC8-type 1)
Nos1  (nitric oxide synthase 1)


Additional Information