ATF3 expression is induced by low glucose in pancreatic alpha and beta cells and regulates glucagon but not insulin gene transcription

作者：Lee Yong Soo; Kobayashi Masaki; Kikuchi Osamu; Sasaki Tsutomu; Yokota Hashimoto Hiromi; Susanti Vina Yanti; Kitamura Yukari Ido; Kitamura Tadahiro^*

来源：Endocrine Journal, 2014, 61(1): 85-90.

DOI：10.1507/endocrj.EJ13-0383

• ATF3
• Glucagon
• Insulin
• Pancreatic a cell
• Pancreatic beta cell

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 alpha and beta 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 alpha TC-1.6 and beta TC3 cells. We also showed that adenovirus-mediated ATF3 overexpression increased glucagon promoter activity and glucagon mRNA levels in alpha TC-1.6 cells; whereas, it had no effect on insulin promoter activity and insulin mRNA levels in beta TC3 cells. Although immunostaining with the C-19 ATF3 antibody demonstrated predominant expression in a cells rather than beta 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 alpha cells and beta 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 alpha cells and beta cells.

• 出版日期2014-1