title: ATF3 expression is induced by low glucose in pancreatic α and β cells and regulates glucagon but not insulin gene transcription.
abstract: The pancreas is critical for maintaining glucose homeostasis. Activating transcription factor 3 (ATF3) is an adaptive response transcription factor. There are major discrepancies in previous reports on pancreatic ATF3; therefore, its role in the pancreas is unclear. To better elucidate the role of ATF3 in the pancreas, we conducted in vitro studies using pancreatic α and β cell lines, and also evaluated the use of ATF3 antibodies for immunohistochemistry. We determined ATF3 expression was increased by low glucose and decreased by high glucose in both αTC-1.6 and βTC3 cells. We also showed that adenovirus-mediated ATF3 overexpression increased glucagon promoter activity and glucagon mRNA levels in αTC-1.6 cells; whereas, it had no effect on insulin promoter activity and insulin mRNA levels in βTC3 cells. Although immunostaining with the C-19 ATF3 antibody demonstrated predominant expression in α cells rather than β cells, ATF3 staining was still detected in ATF3 knockout mice as clearly as in control mice. On the other hand, another ATF3 antibody (H-90) detected ATF3 in both α cells and β cells, and was clearly diminished in ATF3 knockout mice. These results indicate that previous discrepancies in ATF3 expression patterns in the pancreas were caused by the varying specificities of the ATF3 antibodies used, and that ATF3 is actually expressed in both α cells and β cells.
authors.affiliation: Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Osamu
authors.initials: O
authors.lastname: Kikuchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yokota-Hashimoto
authors.forename: Vina Yanti
authors.initials: VY
authors.lastname: Susanti
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ido Kitamura
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D051700:Activating Transcription Factor 3 / Q000032:analysis / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects*; D005934:Glucagon / Q000235:genetics*; D050416:Glucagon-Secreting Cells / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage*; D007328:Insulin / Q000235:genetics*; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D051700:Activating Transcription Factor 3; D007328:Insulin; D012333:RNA, Messenger; D005934:Glucagon; D005947:Glucose