Distribution And Role Of Receptor Interaction Protein 140 In Pancreatic Beta-Cells In Rodents, In Vivo And In Vitro

Objective. This study was to investigate RIP140 expression levels in the pancreas and islet (��-cells in mice and rats and the role of RIP140 in cultured (��-cells using the mouse pancreatic (��-cell line MIN6. Methods. The MIN6 cell line stably overexpressing RIP140 was used. The effects of RIP140 on cell viability, cell cycle, apoptosis, insulin secretion, and its regulated genes were analyzed using flow cytometry, the MTT assay, Western blot analysis, reverse transcriptase (RT)-PCR, and enzyme-linked immunosorbent assay (ELISA). Results. Most of insulin-positive cells in islets expressed RIP140. In MIN6 cells, overexpression of RIP140 inhibited cell viability by reducing the number of cells in S phase and inhibiting proliferating cell nuclear antigen (PCNA) expression. We also found that overexpression of RIP140 inhibited Bcl-2 and mRNA expression of peroxisome proliferator-activated receptor-y coactivator-1a (PGC-1a) and uncoupling protein 2 (UCP2) and increased levels of phosphorylated extracellular signal-regulated protein kinases 1/2 (p-ERK1/2). However, apoptosis rate and levels of basal level of insulin secretion (BIS) and glucose-stimulated insulin (GSIS) were not significantly altered in MIN6 cells. Conclusions. RIP140 was expressed in the pancreas of mice and rats, particularly in ��-cells, and participated in regulating ��-cell function and proliferation.