Conclusions
FFAs can cause reversible impairment of SU-SIS on pancreatic β cells. The reversibility of the effects is partial because of the changes of expression and endocytosis of Kir6.2 and SUR1 which was mediated by dynamin.
Methods
MIN6 cells were treated with PA and OA for 48 h and then washed out for 24 h to determine the changes in expression and endocytosis of the KATP channels and glucose-stimulated insulin secretion (GSIS) and sulfonylurea-stimulated insulin secretion (SU-SIS).
Objective
Lipotoxicity-induced pancreatic β cell-dysfunction
Results
MIN6 cells exposed to PA or OA showed both impaired GSIS and SU-SIS; the former was not restorable, while the latter was reversible with washout of PA or OA. Decreased expressions of both total and surface Kir6.2 and SUR1 and endocytosis of KATP channels were observed, which were also recoverable after washout. When MIN6 cells exposed to free fatty acids (FFAs) were cotreated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or dynasore, we found that endocytosis of KATP channels did not change significantly by AICAR but was almost completely blocked by dynasore. Meanwhile, the inhibition of endocytosis of KATP channels after washout could be activated by PIP2. The recovery of SU-SIS after washout was significantly weakened by PIP2, but the decrease of SU-SIS induced by FFAs was not alleviated by dynasore. Conclusions: FFAs can cause reversible impairment of SU-SIS on pancreatic β cells. The reversibility of the effects is partial because of the changes of expression and endocytosis of Kir6.2 and SUR1 which was mediated by dynamin.