Bachl deficiency protects pancreatic beta-cells from oxidative stress injury

摘要

BTB and CNC limnology 1 (Bachl) is a transcriptional repressor of antioxidative enzymes, such as heme oxygenase-1 (HO-1). Oxidative stress is reportedly involved in insulin secretion impairment and obesity-associated insulin resistance. However, the role of Bachl in the development of diabetes is unclear. HO-1 expression in the liver, white adipose tissue, and pancreatic islets was markedly upregulated in Bachl-deficient mice. Unexpectedly, glucose and insulin tolerance tests showed no differences in obese wild-type (WT) and obese Bach1-deficient mice after high-fat diet loading for 6 wk, suggesting minimal roles of Bachl in the development of insulin resistance. In contrast, Bachl deficiency significantly suppressed alloxan-induced pancreatic insulin content reduction and the resultant glucose elevation. Furthermore, TUNEL-positive cells in pancreatic islets of Bach1-deficient mice were markedly decreased, by 60%, compared with those in WT mice. HO-1 expression in islets was significantly upregulated in alloxan-injected Bachl-deficient mice, whereas expression of other antioxidative enzymes, e.g., catalase, superoxide dismu-tase, and glutathione peroxidase, was not changed by either alloxan administration or Bachl deficiency. Our results suggest that Bachl deficiency protects pancreatic beta-cells from oxidative stress-induced apoptosis and that the enhancement of HO-1 expression plays an important role in this protection.