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 Rutter, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leclerc, I.
Right arrow Articles by Rutter, G. A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:S67-S74, 2004
© 2004 by the American Diabetes Association, Inc.

Section II: Beta-Cell Therapeutic Targets Other Than ATP-Sensitive K+ Channels

AMP-Activated Protein Kinase: A New Beta-Cell Glucose Sensor?

Regulation by Amino Acids and Calcium Ions

Isabelle Leclerc, and Guy A. Rutter

From the Henry Wellcome Laboratories for Integrated Cell Signalling and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, U.K

Stimulation of AMP-activated protein kinase (AMPK) in skeletal muscle and liver is seen as an exciting prospect for the treatment of type 2 diabetes. However, we have recently demonstrated that changes in AMPK activity accompany the exposure of pancreatic islet ß-cells to elevated glucose concentrations and may be involved in the activation of insulin secretion. Here, we discuss this hypothesis and explore the potential role of changes in AMPK activity in the actions of other secretagogues. Amino acids decreased AMPK activity in MIN6 ß-cells with an order of potency for inhibition: arg = leu < gln = leu + glu < glucose, which was closely correlated with the stimulation of insulin release (r2 = 0.76). By contrast, increases in intracellular Ca2+ concentration provoked by cell depolarization with KCl activated AMPK in the face of increased free intracellular ATP concentrations. Elevation of intracellular cAMP levels with isobutylmethyxanthine or forskolin had no effect on AMPK activity. We conclude that metabolizable amino acids regulate AMPK in the ß-cell via increases in the cytosolic ATP/AMP ratio and via phosphorylation by the upstream kinase LKB1. Intracellular Ca2+ ions may activate AMPK by calmodulin kinase 1 kinase-mediated phosphorylation. The latter may act as a novel feedback mechanism to inhibit excessive insulin secretion under some circumstances.

Address correspondence and reprint requests to Professor Guy A. Rutter, Henry Wellcome Laboratories for Integrated Cell Signalling and Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, BS8 1TD Bristol, U.K. E-mail: g.a.rutter{at}bristol.ac.uk


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
 J Mol EndocrinolHome page
H. Ghanaat-Pour, Z. Huang, M. Lehtihet, and A. Sjoholm
Global expression profiling of glucose-regulated genes in pancreatic islets of spontaneously diabetic Goto-Kakizaki rats
J. Mol. Endocrinol., August 1, 2007; 39(2): 135 - 150.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. M. Doliba, S. L. Wehrli, M. Z. Vatamaniuk, W. Qin, C. W. Buettger, H. W. Collins, and F. M. Matschinsky
Metabolic and ionic coupling factors in amino acid-stimulated insulin release in pancreatic beta-HC9 cells
Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1507 - E1519.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. E. Jensen, A. J. Rose, S. B. Jorgensen, N. Brandt, P. Schjerling, J. F. P. Wojtaszewski, and E. A. Richter
Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction
Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1308 - E1317.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. E. Gleason, D. Lu, L. A. Witters, C. B. Newgard, and M. J. Birnbaum
The Role of AMPK and mTOR in Nutrient Sensing in Pancreatic beta-Cells
J. Biol. Chem., April 6, 2007; 282(14): 10341 - 10351.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. Rasouli, P. A Kern, E. A. Reece, and S. C. Elbein
Effects of pioglitazone and metformin on beta-cell function in nondiabetic subjects at high risk for type 2 diabetes
Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E359 - E365.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. L. Hurley, L. K. Barre, S. D. Wood, K. A. Anderson, B. E. Kemp, A. R. Means, and L. A. Witters
Regulation of AMP-activated Protein Kinase by Multisite Phosphorylation in Response to Agents That Elevate Cellular cAMP
J. Biol. Chem., December 1, 2006; 281(48): 36662 - 36672.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
K. Ravnskjaer, M. Boergesen, L. T Dalgaard, and S. Mandrup
Glucose-induced repression of PPAR{alpha} gene expression in pancreatic {beta}-cells involves PP2A activation and AMPK inactivation.
J. Mol. Endocrinol., April 1, 2006; 36(2): 289 - 299.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.