Bach1 deficiency protects pancreatic β-cells from oxidative stress injury

Keiichi Kondo, Yasushi Ishigaki, Junhong Gao, Tetsuya Yamada, Junta Imai, Shojiro Sawada, Akihiko Muto, Yoshitomo Oka, Kazuhiko Igarashi, Hideki Katagiri

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

BTB and CNC homology 1 (Bach1) 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 Bach1 in the development of diabetes is unclear. HO-1 expression in the liver, white adipose tissue, and pancreatic islets was markedly upregulated in Bach1-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 Bach1 in the development of insulin resistance. In contrast, Bach1 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 Bach1-deficient mice, whereas expression of other antioxidative enzymes, e.g., catalase, superoxide dismutase, and glutathione peroxidase, was not changed by either alloxan administration or Bach1 deficiency. Our results suggest that Bach1 deficiency protects pancreatic β-cells from oxidative stress-induced apoptosis and that the enhancement of HO-1 expression plays an important role in this protection.

Original languageEnglish
Pages (from-to)E641-E648
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume305
Issue number5
DOIs
Publication statusPublished - 2013 Sep 17

Keywords

  • Apoptosis
  • BTB and CNC homology 1
  • Diabetes
  • Insulin
  • Oxidative stress
  • Pancreatic
  • β-cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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