RGD Reference Report - NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic ß-cells. - Rat Genome Database

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NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic ß-cells.

Authors:
Citation: Gray JP, etal., Am J Physiol Endocrinol Metab. 2012 Jul 15;303(2):E191-9. doi: 10.1152/ajpendo.00465.2011. Epub 2012 May 1.
RGD ID: 13703105
Pubmed: PMID:22550069   (View Abstract at PubMed)
PMCID: PMC3431206   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpendo.00465.2011   (Journal Full-text)

NADPH is an important component of the antioxidant defense system and a proposed mediator in glucose-stimulated insulin secretion (GSIS) from pancreatic ß-cells. An increase in the NADPH/NADP(+) ratio has been reported to occur within minutes following the rise in glucose concentration in ß-cells. However, 30 min following the increase in glucose, the total NADPH pool also increases through a mechanism not yet characterized. NAD kinase (NADK) catalyzes the de novo formation of NADP(+) by phosphorylation of NAD(+). NAD kinases have been shown to be essential for redox regulation, oxidative stress defense, and survival in bacteria and yeast. However, studies on NADK in eukaryotic cells are scarce, and the function of this enzyme has not been described in ß-cells. We employed INS-1 832/13 cells, an insulin-secreting rat ß-cell line, and isolated rodent islets to investigate the role of NADK in ß-cell metabolic pathways. Adenoviral-mediated overexpression of NADK resulted in a two- to threefold increase in the total NADPH pool and NADPH/NADP(+) ratio, suggesting that NADP(+) formed by the NADK-catalyzed reaction is rapidly reduced to NADPH via cytosolic reductases. This increase in the NADPH pool was accompanied by an increase in GSIS in NADK-overexpressing cells. Furthermore, NADK overexpression protected ß-cells against oxidative damage by the redox cycling agent menadione and reversed menadione-mediated inhibition of GSIS. Knockdown of NADK via shRNA exerted the opposite effect on all these parameters. These data suggest that NADK kinase regulates intracellular redox and affects insulin secretion and oxidative defense in the ß-cell.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
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Original Reference(s)
NadkRatNADP biosynthetic process  IMP  RGD 
NadkRatpositive regulation of insulin secretion involved in cellular response to glucose stimulus  IMP  RGD 


Genes (Rattus norvegicus)
Nadk  (NAD kinase)