Far-infrared radiation prevents decline in β-cell mass and function in diabetic mice via the mitochondria-mediated Sirtuin1 pathway

Insulin deficiency in type 2 diabetes mellitus (DM) involves a decline in both pancreatic beta-cell mass and function. Enhancing beta-cell preservation represents an important therapeutic strategy to treat type 2 DM. Far-infrared (FIR) radiation has been found to induce promyelocytic leukemia zinc finger protein (PLZF) activation to protect the vascular endothelium in diabetic mice. The influence of FIR on beta-cell preservation is unknown. Our previous study reveals that the biologically effective wavelength of FIR is 8-10 mu m. In the present study, we investigated the biological effects of FIR (8-10 mu m) on both survival and insulin secretion function of beta-cells. FIR reduced pancreatic islets loss and increased insulin secretion in nicotinamide-streptozotocin-induced DM mice, but only promoted insulin secretion in DM PLZF(-/-) mice. FIR-upregulated PLZF to induce an anti-apoptotic effect in a beta cell line RIN-m5f. FIR also upregulated mitochondrial function and the ratio of NAD(+)/NADH, and then induced Sirtuin1 (Sirt1) expression. The mitochondria Complex I inhibitor rotenone blocked FIR-induced PLZF and Sirt1. The Sirt1 inhibitor EX527 and Sirt1 siRNA inhibited FIR-induced PLZF and insulin respectively. Sirt1 upregulation also increased Ca(v)1.2 expression and calcium influx that promotes insulin secretion in beta-cells. In summary, FIR-enhanced mitochondrial function prevents beta-cell apoptosis and enhances insulin secretion in DM mice through the Sin 1 pathway. (C) 2020 Elsevier Inc. All rights reserved.