Microcystin-LR induces dysfunction of insulin secretion in rat insulinoma (INS-1) cells: Implications for diabetes mellitus

Microcystins (MCs) are the most frequent cyanobacterial toxins observed in freshwater systems. Accumulating evidence suggests that MCs pose a serious threat to public health. However, the contributions of the exposure of MCs to the occurrence of human diseases remain largely unknown. This study provides the evidence of the effects of MC-LR on pancreatic beta-cell function through the exposure of rat insulinoma (INS-1) cells to 0, 10, 20, or 40 mu M MC-LR for 72 h and explores the underlying molecular mechanisms. Our results demonstrate that exposure to MC-LR for 72 h suppresses cell viability, disturbs glucose-stimulated insulin secretion (GSIS), and decreases the expression of insulin protein. Moreover, MC-LR disrupts the cell cycle distribution and increases cell apoptosis at 20 or 40 mu M for 72 h, respectively, indicating that the beta-cell mass would be decreased by MC-LR exposure. A transcriptomic analysis revealed several key genes (e.g., Pdx-1, Neurodl, and Abcc8) involved in insulin secretion are significantly differentially expressed in INS-1 cells in response to MC-LR exposure. In addition, several signal transduction pathways associated with diabetes (e.g., type 1 and 2 diabetes) were also identified compared with the control cells. We recommend that MC be considered as a new environmental factor that promotes diabetes development. The identified key genes or pathways may potentially contribute to the future therapies in the environmental contaminants induced beta-cell damage. (C) 2016 Elsevier B.V. All rights reserved.