| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans; 2Department of Biology, Xavier University, New Orleans, Louisiana; 3Departments of Pharmacology and Cancer Biology, Medicine, and Biochemistry, Sarah W. Stedman Nutrition and Metabolism Center and Duke University Medical Center, Durham, North Carolina; and 4Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota
Submitted 20 September 2006 ; accepted in final form 9 November 2006
Glucose homeostasis requires the proper expression and regulation of the catalytic subunit of glucose-6-phosphatase (G-6-Pase), which hydrolyzes glucose 6-phosphate to glucose in glucose-producing tissues. Glucose induces the expression of G-6-Pase at the transcriptional and posttranscriptional levels by unknown mechanisms. To better understand this metabolic regulation, we mapped the cis-regulatory elements conferring glucose responsiveness to the rat G-6-Pase gene promoter in glucose-responsive cell lines. The full-length (–4078/+64) promoter conferred a moderate glucose response to a reporter construct in HL1C rat hepatoma cells, which was dependent on coexpression of glucokinase. The same construct provided a robust glucose response in 832/13 INS-1 rat insulinoma cells, which are not glucogenic. Glucose also strongly increased endogenous G-6-Pase mRNA levels in 832/13 cells and in rat pancreatic islets, although the induced levels from islets were still markedly lower than in untreated primary hepatocytes. A distal promoter region was glucose responsive in 832/13 cells and contained a carbohydrate response element with two E-boxes separated by five base pairs. Carbohydrate response element-binding protein bound this region in a glucose-dependent manner in situ. A second, proximal promoter region was glucose responsive in both 832/13 and HL1C cells, with a hepatocyte nuclear factor 1 binding site and two cAMP response elements required for glucose responsiveness. Expression of dominant-negative versions of both cAMP response element-binding protein and CAAT/enhancer-binding protein blocked the glucose response of the proximal region in a dose-dependent manner. We conclude that multiple, distinct cis-regulatory promoter elements are involved in the glucose response of the rat G-6-Pase gene.
glucose-6-phosphatase; promoter; carbohydrate response element; carbohydrate response element-binding protein; adenosine 3',5'-cyclic monophosphate response element
This article has been cited by other articles:
|
|
 |
|
  A. Perilhou, C. Tourrel-Cuzin, P. Zhang, I. Kharroubi, H. Wang, V. Fauveau, D. K. Scott, C. B. Wollheim, and M. Vasseur-Cognet The MODY1 Gene for Hepatocyte Nuclear Factor 4{alpha} and a Feedback Loop Control COUP-TFII Expression in Pancreatic Beta Cells Mol. Cell. Biol., July 15, 2008; 28(14): 4588 - 4597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Han, D. L. Hagan, J. R. Taylor, L. Xin, W. Meng, S. A. Biller, J. R. Wetterau, W. N. Washburn, and J. M. Whaley Dapagliflozin, a Selective SGLT2 Inhibitor, Improves Glucose Homeostasis in Normal and Diabetic Rats Diabetes, June 1, 2008; 57(6): 1723 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dentin, S. Hedrick, J. Xie, J. Yates III, and M. Montminy Hepatic Glucose Sensing via the CREB Coactivator CRTC2 Science, March 7, 2008; 319(5868): 1402 - 1405. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
