Vitamin D decreases pancreatic iron overload in type 2 diabetes through the NF-κB-DMT1 pathway

Abstract

Emerging evidence has deemed vitamin D as a potential candidate for the intervention of type 2 diabetes (T2D). Herein, we explored the underlying mechanisms of T2D prevention by vitamin D, concentrating on pancreatic iron deposition reported recently. Zucker diabetic fatty (ZDF) rats were treated by vitamin D, with age-matched Zucker lean rats as control. As expected, vitamin D treatment for ZDF rats normalized islet morphology and β-cell function. Moreover, vitamin D alleviated iron accumulation and apoptosis in pancreatic cells of ZDF rats, accompanied by lowered divalent metal transporter 1 (DMT1) expression. Consistently, similar results were observed in high glucose-stimulated INS-1 cells treated with or without vitamin D. Nuclear factor-κB (NF-κB), a transcription factor involving DMT1 regulation, was activated in pancreases of ZDF rats and INS-1 cells exposed to high glucose, but inactivated by vitamin D or BAY 11-7082, a NF-κB inhibitor. Futhermore, IL-1β functioning as NF-κB activator abolished the suppression of NF-κB activation, DMT1 induction and the attenuation of apoptosis as a consequence of vitamin D incubation. Our study showed that iron overload in pancreas may contribute to T2D pathogenesis and uncovered a potentially protective role for vitamin D on iron deposition of diabetic pancreas through NF-κB- DMT1 signaling.