Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leclerc, I.
Right arrow Articles by Viollet, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leclerc, I.
Right arrow Articles by Viollet, B.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes 50:1515-1521, 2001
© 2001 by the American Diabetes Association, Inc.

Hepatocyte Nuclear Factor-4{alpha} Involved in Type 1 Maturity-Onset Diabetes of the Young Is a Novel Target of AMP-Activated Protein Kinase

Isabelle Leclerc, Claudia Lenzner, Laurence Gourdon, Sophie Vaulont, Axel Kahn, and Benoît Viollet

Cochin Institute of Molecular Genetics, Department of Genetics, Development, and Molecular Pathology, Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 129, Paris, France

Mutations in the HNF4{alpha} gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. Hepatocyte nuclear factor (HNF)-4{alpha} is a transcription factor that plays a critical role in the transcriptional regulation of genes involved in glucose metabolism in both hepatocytes and pancreatic ß-cells. Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic ß-cells and the control of glucose-dependent gene expression in both hepatocytes and ß-cells. Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4{alpha} function. In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4{alpha} protein levels and consequently downregulates the expression of HNF-4{alpha} target genes. Quantitative evaluation of HNF-4{alpha} target gene expression revealed diminished mRNA levels for HNF-1{alpha}, GLUT2, L-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. Our data clearly demonstrate that the MODY1/HNF-4{alpha} transcription factor is a novel target of AMPK in hepatocytes. Accordingly, it can be suggested that in pancreatic ß-cells, AMPK also acts by decreasing HNF-4{alpha} protein level, and therefore insulin secretion. Hence, the possible role of AMPK in the physiopathology of type 2 diabetes should be considered.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Circ. Res.Home page
M. C. Towler and D. G. Hardie
AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
Circ. Res., February 16, 2007; 100(3): 328 - 341.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Shin, I. Kim, Y. Inoue, S. Kimura, and F. J. Gonzalez
Regulation of Mouse Hepatic {alpha}-Amino-beta-Carboxymuconate-{epsilon}-Semialdehyde Decarboxylase, a Key Enzyme in the Tryptophan-Nicotinamide Adenine Dinucleotide Pathway, by Hepatocyte Nuclear Factor 4{alpha} and Peroxisome Proliferator-Activated Receptor {alpha}
Mol. Pharmacol., October 1, 2006; 70(4): 1281 - 1290.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
B. Viollet, M. Foretz, B. Guigas, S. Horman, R. Dentin, L. Bertrand, L. Hue, and F. Andreelli
Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders
J. Physiol., July 1, 2006; 574(1): 41 - 53.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Peignon, S. Thenet, C. Schreider, S. Fouquet, A. Ribeiro, E. Dussaulx, J. Chambaz, P. Cardot, M. Pincon-Raymond, and J. Le Beyec
E-cadherin-dependent Transcriptional Control of Apolipoprotein A-IV Gene Expression in Intestinal Epithelial Cells: A ROLE FOR THE HEPATIC NUCLEAR FACTOR 4
J. Biol. Chem., February 10, 2006; 281(6): 3560 - 3568.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
X. Prieur, F. G. Schaap, H. Coste, and J. C. Rodriguez
Hepatocyte Nuclear Factor-4{alpha} Regulates the Human Apolipoprotein AV Gene: Identification of a Novel Response Element and Involvement in the Control by Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1{alpha}, AMP-Activated Protein Kinase, and Mitogen-Activated Protein Kinase Pathway
Mol. Endocrinol., December 1, 2005; 19(12): 3107 - 3125.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. Foretz, N. Ancellin, F. Andreelli, Y. Saintillan, P. Grondin, A. Kahn, B. Thorens, S. Vaulont, and B. Viollet
Short-Term Overexpression of a Constitutively Active Form of AMP-Activated Protein Kinase in the Liver Leads to Mild Hypoglycemia and Fatty Liver
Diabetes, May 1, 2005; 54(5): 1331 - 1339.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. Jahan and J. Y. L. Chiang
Cytokine regulation of human sterol 12{alpha}-hydroxylase (CYP8B1) gene
Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G685 - G695.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
I. Leclerc and G. A. Rutter
AMP-Activated Protein Kinase: A New Beta-Cell Glucose Sensor?: Regulation by Amino Acids and Calcium Ions
Diabetes, December 1, 2004; 53(suppl_3): S67 - S74.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
D. G. Hardie
The AMP-activated protein kinase pathway - new players upstream and downstream
J. Cell Sci., November 1, 2004; 117(23): 5479 - 5487.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
I. Leclerc, W. W. Woltersdorf, G. da Silva Xavier, R. L. Rowe, S. E. Cross, G. S. Korbutt, R. V. Rajotte, R. Smith, and G. A. Rutter
Metformin, but not leptin, regulates AMP-activated protein kinase in pancreatic islets: impact on glucose-stimulated insulin secretion
Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E1023 - E1031.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
D. Sauvaget, V. Chauffeton, S. Dugue-Pujol, A.-D. Kalopissis, I. Guillet-Deniau, F. Foufelle, J. Chambaz, A. Leturque, P. Cardot, and A. Ribeiro
In Vitro Transcriptional Induction of the Human Apolipoprotein A-II Gene by Glucose
Diabetes, March 1, 2004; 53(3): 672 - 678.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Yu, N. Fujii, M. F. Hirshman, J. M. Pomerleau, and L. J. Goodyear
Cloning and characterization of mouse 5'-AMP-activated protein kinase {gamma}3 subunit
Am J Physiol Cell Physiol, February 1, 2004; 286(2): C283 - C292.
[Abstract] [Full Text]

Home page
 Protein Sci.Home page
J. Adams, Z.-P. Chen, B. J.W. Van Denderen, C. J. Morton, M. W. Parker, L. A. Witters, D. Stapleton, and B. E. Kemp
Intrasteric control of AMPK via the {gamma}1 subunit AMP allosteric regulatory site
Protein Sci., January 1, 2004; 13(1): 155 - 165.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. G. Hardie
Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status
Endocrinology, December 1, 2003; 144(12): 5179 - 5183.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. H. Hong, U. S. Varanasi, W. Yang, and T. Leff
AMP-activated Protein Kinase Regulates HNF4{alpha} Transcriptional Activity by Inhibiting Dimer Formation and Decreasing Protein Stability
J. Biol. Chem., July 18, 2003; 278(30): 27495 - 27501.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. K. T. Lam, A. Carpentier, G. F. Lewis, G. van de Werve, I. G. Fantus, and A. Giacca
Mechanisms of the free fatty acid-induced increase in hepatic glucose production
Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E863 - E873.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Eto, T. Yamashita, J. Matsui, Y. Terauchi, M. Noda, and T. Kadowaki
Genetic Manipulations of Fatty Acid Metabolism in {beta}-Cells Are Associated With Dysregulated Insulin Secretion
Diabetes, December 1, 2002; 51(90003): S414 - 420.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. Kawaguchi, K. Osatomi, H. Yamashita, T. Kabashima, and K. Uyeda
Mechanism for Fatty Acid "Sparing" Effect on Glucose-induced Transcription. REGULATION OF CARBOHYDRATE-RESPONSIVE ELEMENT-BINDING PROTEIN BY AMP-ACTIVATED PROTEIN KINASE
J. Biol. Chem., February 1, 2002; 277(6): 3829 - 3835.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2001 by the American Diabetes Association.