The role of interleukin‐1β and extracellular signal‐regulated kinase 1/2 in glucose‐stimulated insulin secretion

Abstract

Glucose-stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet β cells, and extracellular-regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen-activated protein kinase family that regulates this process. The inflammatory cytokine interleukin (IL)-1β can inhibit the insulin secretion of pancreatic β cells, but the exact mechanism is unclear. This study was designed to investigate the inhibitory effect of IL-1β on GSIS in βTC-6 cells and its relation with the ERK1/2 signal transduction pathway. β-TC6 cells were cultured and stimulated with 0mM, 1.38mM, or 5.5mM glucose. In addition, GSIS in β-TC6 cells was blocked by IL-1β at concentrations of 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL. After glucose stimulation and IL-1β intervention, the insulin level in the cell supernatant was detected by radioimmunoassay, and the phosphorylation level of ERK1/2 was detected by western blotting assay. The insulin level in the 1.38mM glucose group was 108.52 ± 5.94 uIU/mL, which was significantly higher than the 0mM and 5.5mM glucose groups (p < 0.05). Compared with the 0mM glucose group, the level of ERK1/2 phosphorylation was increased in the 1.38mM and 5.5mM glucose groups. After intervention by 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL IL-1β, the level of ERK1/2 phosphorylation induced by 1.38mM glucose stimulation decreased in a dose-dependent manner, and the insulin level correspondingly decreased. IL-1β can inhibit GSIS in βTC-6 cells, which is related to its inhibition of the phosphorylation of ERK1/2.

Perfluoroalkyl Substances Stimulate Insulin Secretion by Islet β Cells via G Protein-Coupled Receptor 40

“…Our results showed that 1.4 mM glucose had the highest activity in the GSIS of β-TC-6 cells with 1.7-fold higher than the control group (Figure S7A). This result was consistent with a previous study showing that β-TC-6 cells were more sensitive to 1.4 mM glucose …”

“…β-TC-6 cells (3 × 10 5 cells/mL) were seeded in 24-well plates and allowed to adhere for 48 h. Cells were changed into Krebs-Ringer bicarbonate HEPES buffer (KRBH, Leagene, China) with or without 0.1% bovine serum albumin (BSA) for 30 min. Then, the supernatant was removed and replaced by new assay buffer containing different concentration of glucose (Sigma, USA) and tested chemicals in KRBH buffer (with or without 0.1% BSA) for 60 min . Next, the supernatant of each well was collected into a new tube separately; cells that adhered on the bottom of each well were lysed by RIPA (Solarbio, China) for 20 min and then the cell lysate of each well was collected into another tube.…”

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

“…Weaver et al (36) revealed that GSiS was attenuated by the inflammatory cytokines TNF-α, il-1β and IFN-γ, but protected by the nadPH-1 oxidase-1 inhibitor Ml171 in isolated mouse islets and murine β cell lines. Our previous study found that il-1β and/or IFN-γ inhibited insulin secretion by βTc-6 cells in a glucose stimulation test with a synergistic effect, and the inhibitory effect of il-1β on GSiS was dose-dependent (15). The present study revealed similar results in Min6 cells.…”

“…our previous studies showed that the optimal concentration of glucose for the stimulation of βTC-6 cells was 1.38 mmol/l, but the peak value of insulin secretion after stimulation was only 26% higher than the base value (14,15). Min6 pancreatic β cells are more sensitive to glucose than βTc-6 cells in the study of insulin secretion (16).…”

“…Previous studies have focused on only one or two pathways (7)(8)(9)(10)(11)(12)(13) and the role of the MaPK signaling system is not yet fully understood. in our previous studies, it was found that il-1β inhibited the secretion of insulin under glucose stimulation in βTc-6 cells, and the mechanism of insulin secretion was associated with the inhibition of ERK1/2 (14,15). However, in those studies, only the effect of il-1β on the ERK1/2 pathway was examined and the roles of JnK and p38 signaling pathways in the insulin secretory function of pancreatic β cells remain unclear.…”