| First Author | Kondo T | Year | 2012 |
| Journal | Diabetes | Volume | 61 |
| Issue | 4 | Pages | 838-47 |
| PubMed ID | 22362176 | Mgi Jnum | J:196732 |
| Mgi Id | MGI:5489828 | Doi | 10.2337/db11-1098 |
| Citation | Kondo T, et al. (2012) Hyperthermia with mild electrical stimulation protects pancreatic beta-cells from cell stresses and apoptosis. Diabetes 61(4):838-47 |
| abstractText | Induction of heat shock protein (HSP) 72 improves metabolic profiles in diabetic model mice. However, its effect on pancreatic beta-cells is not known. The current study investigated whether HSP72 induction can reduce beta-cell stress signaling and apoptosis and preserve beta-cell mass. MIN6 cells and db/db mice were sham-treated or treated with heat shock (HS) and mild electrical stimulation (MES) (HS+MES) to induce HSP72. Several cellular markers, metabolic parameters, and beta-cell mass were evaluated. HS+MES treatment or HSP72 overexpression increased HSP72 protein levels and decreased tumor necrosis factor (TNF)-alpha-induced Jun NH(2)-terminal kinase (JNK) phosphorylation, endoplasmic reticulum (ER) stress, and proapoptotic signal in MIN6 cells. In db/db mice, HS+MES treatment for 12 weeks significantly improved insulin sensitivity and glucose homeostasis. Upon glucose challenge, a significant increase in insulin secretion was observed in vivo. Compared with sham treatment, levels of HSP72, insulin, pancreatic duodenal homeobox-1, GLUT2, and insulin receptor substrate-2 were upregulated in the pancreatic islets of HS+MES-treated mice, whereas JNK phosphorylation, nuclear translocation of forkhead box class O-1, and nuclear factor-kappaB p65 were reduced. Apoptotic signals, ER stress, and oxidative stress markers were attenuated. Thus, HSP72 induction by HS+MES treatment protects beta-cells from apoptosis by attenuating JNK activation and cell stresses. HS+MES combination therapy may preserve pancreatic beta-cell volume to ameliorate glucose homeostasis in diabetes. |
