The use of transgenic mice to analyze the role of accessory factor two in the regulation of phosphoenolpyruvate carboxykinase (GTP) gene transcription during diabetes

The Journal of Biological Chemistry
P S LechnerR W Hanson

Abstract

The regulation of transcription of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (4.1.1.32) during diabetes is a complex process that involves a number of regulatory elements in the PEPCK-C gene promoter. The accessory factor 2 (AF2)-binding region that is contained within the glucocorticoid regulatory unit of the PEPCK-C gene promoter (-451 to -353) has been implicated in the action of both insulin and glucocorticoids on PEPCK-C gene transcription. To determine the role of AF2 in these processes, we have generated a mouse model bearing a transgene that contains the PEPCK-C gene promoter with a mutation in the AF2-binding region. This promoter is linked to the structural gene for human growth hormone that is biologically inactive (AF2-2000/hGx). In the absence of the AF2 regulatory element, the transcription of the transgene in the liver is not induced by diabetes but is inhibited by the administration of insulin. There is also a marked reduction in the response of the AF2-2000/hGx gene in the kidney to the administration of glucocorticoids. The AF2-2000/hGx gene in the liver responds normally to a high carbohydrate diet with a marked decrease in gene transcription. This suggests that insu...Continue Reading

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Citations

May 27, 2005·Critical Reviews in Biochemistry and Molecular Biology·Kaushik ChakravartyRichard W Hanson
Jan 28, 2004·The Journal of Biological Chemistry·Kaushik ChakravartyRichard W Hanson
May 29, 2008·American Journal of Physiology. Endocrinology and Metabolism·Dipanjan ChandaHueng-Sik Choi
Nov 24, 2004·The Journal of Biological Chemistry·Richard W Hanson
Sep 17, 2005·The Journal of Biological Chemistry·Jianqi YangRichard W Hanson
Jan 11, 2021·Journal of Endocrinological Investigation·W-X SunS-G Pang

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