The adipocytokine Nampt and its product NMN have no effect on beta-cell survival but potentiate glucose stimulated insulin secretion

• Published in: PloS one Vol. 8; no. 1; p. e54106
• Main Authors: Spinnler, Robert, Gorski, Theresa, Stolz, Katharina, Schuster, Susanne, Garten, Antje, Beck-Sickinger, Annette G, Engelse, Marten A, de Koning, Eelco J P, Körner, Antje, Kiess, Wieland, Maedler, Kathrin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.01.2013; Public Library of Science (PLoS)
• Subjects: Acute effects; Adenylate kinase; Adiponectin - metabolism; Adipose tissue; Animals; Annexin V; Apoptosis; Apoptosis - drug effects; Beta cells; Biology; Blotting, Western; Cell culture; Cell survival; Cell Survival - drug effects; Chronic conditions; Chronic illnesses; Cytokines; Cytotoxicity; Diabetes mellitus; Enzymes; Glucose; Glucose - pharmacology; Humans; IL-1β; Incubation; Insulin; Insulin - metabolism; Insulin resistance; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Interferon; Leptin - metabolism; Medicine; Molecular interactions; Niacinamide; Nicotinamide; Nicotinamide phosphoribosyltransferase; Nicotinamide Phosphoribosyltransferase - pharmacology; Obesity; Palmitic acid; Pancreatic beta cells; Phosphoribosyltransferase; Rats; Rodents; Signaling; Survival; Toxicity; Tumor necrosis factor-α; Type 2 diabetes; Womens health; γ-Interferon; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0054106

Obesity is associated with a dysregulation of beta-cell and adipocyte function. The molecular interactions between adipose tissue and beta-cells are not yet fully elucidated. We investigated, whether or not the adipocytokine Nicotinamide phosphoribosyltransferase (Nampt) and its enzymatic product Nicotinamide mononucleotide (NMN), which has been associated with obesity and type 2 diabetes mellitus (T2DM) directly influence beta-cell survival and function. The effect of Nampt and NMN on viability of INS-1E cells was assessed by WST-1 assay. Apoptosis was measured by Annexin V/PI and TUNEL assay. Activation of apoptosis signaling pathways was evaluated. Adenylate kinase release was determined to assess cytotoxicity. Chronic and acute effects of the adipocytokine Nampt and its enzymatic product NMN on insulin secretion were assessed by glucose stimulated insulin secretion in human islets. While stimulation of beta-cells with the cytokines IL-1β, TNFα and IFN-γ or palmitate significantly decreased viability, Nampt and NMN showed no direct effect on viability in INS-1E cells or in human islets, neither alone nor in the presence of pro-diabetic conditions (elevated glucose concentrations and palmitate or cytokines). At chronic conditions over 3 days of culture, Nampt and its product NMN had no effects on insulin secretion. In contrast, both Nampt and NMN potentiated glucose stimulated insulin secretion acutely during 1 h incubation of human islets. Nampt and NMN neither influenced beta-cell viability nor apoptosis but acutely potentiated glucose stimulated insulin secretion.