ArticleAmerican journal of physiology. Endocrinology and metabolism2012
NAD kinase regulates the size of the NADPH pool and insulin secretion in pancreatic β-cells.
Article in American journal of physiology. Endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- NMRK2-YAP-NADK axis preserves redox protection against myocardial ischemia/reperfusion injury.Redox biology · 2026Article
- i-Motif, not G-quadruplex, stability regulates insulin expression.Nucleic acids research · 2026Article
- Keeping up with the nicotinamides: NADP(H), the forgotten circadian cofactor that keeps metabolic time.Life metabolism · 2025Review
- Serum proteins and faecal microbiota as potential biomarkers in newly diagnosed, treatment-naïve inflammatory bowel disease and irritable bowel syndrome patients.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Downregulation of NAD Kinase Expression in β-Cells Contributes to the Aging-Associated Decline in Glucose-Stimulated Insulin Secretion.Aging cell · 2025Article
- Homeostatic regulation of NAD(H) and NADP(H) in cells.Genes & diseases · 2024Review
- NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus.International journal of molecular sciences · 2023Review
- Apollo-NADPScience advances · 2023Article
- Prioritization of genes associated with type 2 diabetes mellitus for functional studies.Nature reviews. Endocrinology · 2023Review
- (-)-Epigallocatechin Gallate is a Noncompetitive Inhibitor of NAD Kinase.ACS medicinal chemistry letters · 2022Article
- Kinetic and data-driven modeling of pancreatic β-cell central carbon metabolism and insulin secretion.PLoS computational biology · 2022Article
- A general strategy to red-shift green fluorescent protein-based biosensors.Nature chemical biology · 2020Article
- NAD- and NADPH-Contributing Enzymes as Therapeutic Targets in Cancer: An Overview.Biomolecules · 2020Review
- The NAD kinase OsNADK1 affects the intracellular redox balance and enhances the tolerance of rice to drought.BMC plant biology · 2020Article
- Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin.Cancers · 2019Article
- Biochemical and physiological properties of KChemico-biological interactions · 2019Review
- Calmodulin Is the Fundamental Regulator of NADK-Mediated NAD Signaling in Plants.Frontiers in plant science · 2019Article
- NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.Antioxidants & redox signaling · 2018Review
- NAD Kinases: Metabolic Targets Controlling Redox Co-enzymes and Reducing Power Partitioning in Plant Stress and Development.Frontiers in plant science · 2018Review
- Mechanisms of the amplifying pathway of insulin secretion in the β cell.Pharmacology & therapeutics · 2017Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
NADPH is an important component of the antioxidant defense system and a proposed mediator in glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. An increase in the NADPH/NADP(+) ratio has been reported to occur within minutes following the rise in glucose concentration in β-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 β-cells. We employed INS-1 832/13 cells, an insulin-secreting rat β-cell line, and isolated rodent islets to investigate the role of NADK in β-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 β-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 β-cell.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.