title: Bach1 deficiency protects pancreatic β-cells from oxidative stress injury.
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.
authors.affiliation: Division of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan;
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kondo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Junhong
authors.initials: J
authors.lastname: Gao
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Junta
authors.initials: J
authors.lastname: Imai
authors.forename: Shojiro
authors.initials: S
authors.lastname: Sawada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Muto
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Igarashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000201:enzymology / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006651:Histocytochemistry; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D051547:Heme Oxygenase-1
keywords: BTB and CNC homology 1; apoptosis; diabetes; insulin; oxidative stress; pancreatic β-cells