Effect of sitagliptin on lipopolysaccharide-induced changes in the mass and function of islet β cells

Abstract

Objective To investigate the effect of dipeptidyl peptidase-4(DPP-4)inhibitor on lipopolysaccharide(LPS)-induced changes in the mass and function of pancreatic β-cells. Methods RINm cells were cultured and treated with LPS alone or combined with different concentrations of sitagliptin for 24 h. The proliferation of RINm cells was detected by CCK-8 assay. Apoptotic rate was determined by Annexin V-fluorescein isothiocyanate(FITC)/propidium iodide flow cytometry. Insulin secretion was measured by enzyme-linked immunosorbent assay. The expression of IL-6 mRNA was displayed by RT-PCR. Results LPS significantly stimulated the proliferation of RINm cells(0.89±0.04 vs 1.14±0.08, P<0.01), while LPS+ sitagliptin showed no significant difference compared with LPS group. The cell apoptotic rate in LPS+ 10-1mmol/L sitagliptin group was significantly lower than that in LPS group. There were no significant differences in basal insulin secretion among all groups, but after the high/low glucose stimulation, LPS increased insulin secretion as compared with the control. The IL-6 mRNA expression in LPS+ sitagliptin group was significantly lower than that in LPS group(0.77±0.33 vs 1.30±0.41, P=0.006). Conclusions DPP-4 inhibitor has no influence on LPS-induced proliferation of pancreatic β-cell, but it can inhibit LPS-induced apoptosis and insulin secretion, and IL-6 may be involved in the process. (Chin J Endocrinol Metab, 2015, 31: 447-451) Key words: Dipeptidyl peptidase-4 inhibitor; Lipopolysaccharide; Pancreatic β-cell