Hyperthermia with Mild Electrical Stimulation Protects Pancreatic β-Cells From Cell Stresses and Apoptosis

Induction of heat shock protein (HSP) 72 improves metabolic profiles in diabetic model mice.However, its impact on pancreatic β-cells is not known. The present study investigated whetherHSP72 induction can reduce β-cell stress signaling and apoptosis, and preserve β-cell mass.MIN6 cells and db/db mice were sham-treated or treated with heat shock (HS) + mild electricalstimulation (MES) to induce HSP72. Several cellular markers, metabolic parameters and β-cellmass were evaluated.HS+MES treatment or HSP72 overexpression increased the HSP72 protein levels and decreasedTNF-β-induced JNK phosphorylation, ER stress and pro-apoptotic signal in MIN6 cells. In db/dbmice, HS+MES treatment for 12 weeks significantly improved the insulin sensitivity and glucosehomeostasis. Upon glucose challenge, a significant increase in insulin secretion was observed invivo. Compared with sham treatment, the HSP72, insulin, PDX-1, GLUT2 and IRS-2 levels wereupregulated in the pancreatic islets of HS+MES-treated mice, whereas JNK phosphorylation,nuclear translocation of FOXO1 and NF-βB p65 were reduced. Apoptotic signals, ER stress andoxidative stress markers were attenuated.Thus, HSP72 induction by HS+MES treatment protects β-cells from apoptosis by attenuatingJNK activation and cell stresses. HS+MES combination therapy may preserve pancreatic β-cellvolume to ameliorate glucose homeostasis in diabetes