Glucagon-like peptide-1 receptor agonist exendin-4 protects against interleukin-1β-mediated inhibition of glucose-stimulated insulin secretion by mouse insulinoma β cells
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- Published online on: July 19, 2017 https://doi.org/10.3892/etm.2017.4803
- Pages: 2671-2676
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Abstract
The aim of the present study was to investigate the protective effect of the glucagon‑like peptide‑1 receptor agonist exendin‑4 on the interleukin (IL)‑1β‑induced impairment of glucose‑stimulated insulin secretion (GSIS) in β‑TC‑6 cells. β‑TC‑6 cells were pretreated with various concentrations of IL‑1β (0.15, 1.5 or 15 ng/ml) and exendin‑4 (0.1 or 1 mM). Exendin‑4 was administered to β‑TC‑6 cells prior to, during and following pretreatment. Cells were stimulated with various concentrations of glucose (0, 1.38, 5.5 and 11.1 mM), and insulin was measured via radioimmunoassay of the supernatant; furthermore, western blot analysis was used to detect phosphorylated extracellular receptor kinase (ERK)1/2. The insulin levels (151.08±14.34 µIU/ml) and ERK1/2 phosphorylation in β‑TC‑6 cells peaked in response to 1.38 mM glucose stimulation compared with 0, 5.5 and 11.1 mM glucose stimulation. IL‑1β inhibited GSIS in a dose‑dependent manner: Insulin levels were 83.76±1.16 µIU/ml when 0.15 ng/ml IL‑1β was added under GSIS, 59.46±3.20 µIU/ml when 1.5 ng/ml IL‑1β was added under GSIS, and 56.98±1.19 µIU/ml when 15 ng/ml IL‑1β was added under GSIS. Exendin‑4 exerted a protective effect against IL‑1β‑induced GSIS inhibition in a dose‑dependent manner. The greatest protective effect was observed when exendin‑4 was added prior to IL‑1β pretreatment, which was statistically significant (P<0.05). These findings suggested that exendin‑4 was able to reverse the IL‑1β‑induced inhibition of ERK1/2 phosphorylation and serves a protective role by impairing GSIS induced by IL‑1β in β‑TC‑6 cells. This mechanism may be associated with the recovery of ERK1/2 activation.
