Effekte von Adipozytokinen auf INS-1E Beta-Zellen

ABSTRACT Aims/hypothesis: 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), which has been associated with obesity and type 2 diabetes mellitus (T2DM) directly influences beta-cell survival and function. Methods: The effect of Nampt 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 nicotinamide mononucleotide (NMN) on insulin secretion were assessed by glucose stimulated insulin secretion in human islets. Results: While stimulation of beta-cells with the cytokines IL-1β, TNFα and IFN-γ or palmitate significantly decreased viability, Nampt 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 1h incubation of human islets. Conclusion/interpretation: Nampt did influence neither beta-cell viability nor apoptosis but acutely potentiated glucose stimulated insulin secretion