Different MAPK signal transduction pathways play different roles in the impairment of glucose-stimulated insulin secretion in response to IL-1β.

Mitogen-activated protein kinase (MAPK) signal transduction pathways may be involved in the destruction of pancreatic islet β cells induced by inflammatory cytokines. The present study aimed to investigate the role of different MAPK signal transduction pathways in the interleukin-1β (IL-1β)-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 mouse pancreatic cells. Min6 cells were stimulated with different concentrations of glucose (0.0, 5.5, 11.1 and 22.2 mmol/l), or different concentrations of IL-1β (0.00, 0.25 and 2.50 ng/ml) in combination with high glucose (22.2 mmol/l) and the culture supernatant was collected. The concentration of insulin was measured by enzyme-linked immunosorbent assay and the activation of different MAPK pathways was assessed by measuring the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) via western blotting. The production of reactive oxygen species (ROS) was determined via flow cytometry, and cell viability was detected by Cell Counting Kit-8 assay. Reverse transcription-quantitative PCR was used to detect the insulin 1 gene. The results revealed that glucose activated ERK1/2 phosphorylation, but inhibited JNK and p38 phosphorylation in a concentration-dependent manner. Furthermore, IL-1β inhibited glucose-stimulated insulin secretion in a dose-dependent manner. Western blotting revealed that IL-1β inhibited the activation of ERK1/2 phosphorylation and attenuated the inhibition of p38 phosphorylation induced by glucose stimulation. JNK was neither activated nor inhibited by IL-1β. These results suggest that MAPK signal transduction pathways participated in the IL-1β-induced GSIS inhibition in Min6 cells, with the ERK1/2, JNK and p38 signaling pathways playing different roles. [ABSTRACT FROM AUTHOR]