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 Pencek, R. R.
Right arrow Articles by Wasserman, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pencek, R. R.
Right arrow Articles by Wasserman, D. H.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 54:355-360, 2005
© 2005 by the American Diabetes Association, Inc.

5-Aminoimidazole-4-Carboxamide-1-ß-D-Ribofuranoside Causes Acute Hepatic Insulin Resistance In Vivo

R. Richard Pencek, Jane Shearer, Raul C. Camacho, Freyja D. James, D. Brooks Lacy, Patrick T. Fueger, E. Patrick Donahue, Wanda Snead, and David H. Wasserman

From the Department of Molecular Physiology and Biophysics, Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee

The infusion of 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) causes a rise in tissue concentrations of the AMP analog 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranotide (ZMP), which mimics an elevation of cellular AMP levels. The purpose of this work was to determine the effect of raising hepatic ZMP levels on hepatic insulin action in vivo. Dogs had sampling and infusion catheters as well as flow probes implanted 16 days before an experiment. After an 18-h fast, blood glucose was 82 ± 1 mg/dl and basal net hepatic glucose output 1.5 ± 0.2 mg · kg–1 · min–1. Dogs received portal venous glucose (3.2 mg · kg–1 · min–1), peripheral venous somatostatin, and basal portal venous glucagon infusions from –90 to 60 min. Physiological hyperinsulinemia was established with a portal insulin infusion (1.2 mU · kg–1 · min–1). Peripheral venous glucose infusion was used to clamp arterial blood glucose at 150 mg/dl. Starting at t = 0 min, dogs received portal venous AICAR infusions of 0, 1, or 2 mg · kg–1 · min–1. Net hepatic glucose uptake was 2.4 ± 0.5 mg · kg–1 · min–1 (mean of all groups) before t = 0 min. In the absence of AICAR, net hepatic glucose uptake was 1.9 ± 0.4 mg · kg–1 · min–1 at t = 60 min. The lower-dose AICAR infusion caused a complete suppression of net hepatic glucose uptake (–1.0 ± 1.7 mg · kg–1 · min–1 at t = 60 min). The higher AICAR dose resulted in a profound shift in hepatic glucose balance from net uptake to a marked net output (–6.1 ± 1.9 mg · kg–1 · min–1 at t = 60 min), even in the face of hyperglycemia and hyperinsulinemia. These data show that elevations in hepatic ZMP concentrations, induced by portal venous AICAR infusion, cause acute hepatic insulin resistance. These findings have important implications for the targeting of AMP kinase for the treatment of insulin resistance, using AMP analogs.

Address correspondence and reprint requests to Richard Pencek, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615. E-mail: pencekr{at}dom.pitt.edu

Abbreviations: ACC, acetyl CoA carboxylase; AICAR, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside; NEFA, nonesterified fatty acid; ZMP, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranotide


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
 DiabetesHome page
D. J. Cuthbertson, J. A. Babraj, K. J.W. Mustard, M. C. Towler, K. A. Green, H. Wackerhage, G. P. Leese, K. Baar, M. Thomason-Hughes, C. Sutherland, et al.
5-Aminoimidazole-4-Carboxamide 1-{beta}-D-Ribofuranoside Acutely Stimulates Skeletal Muscle 2-Deoxyglucose Uptake in Healthy Men
Diabetes, August 1, 2007; 56(8): 2078 - 2084.
[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
 DiabetesHome page
B. Guigas, L. Bertrand, N. Taleux, M. Foretz, N. Wiernsperger, D. Vertommen, F. Andreelli, B. Viollet, and L. Hue
5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside and Metformin Inhibit Hepatic Glucose Phosphorylation by an AMP-Activated Protein Kinase-Independent Effect on Glucokinase Translocation.
Diabetes, April 1, 2006; 55(4): 865 - 874.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. C. Camacho, E. P. Donahue, F. D. James, E. D. Berglund, and D. H. Wasserman
Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice
Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E405 - E408.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
R. C. Camacho, D. B. Lacy, F. D. James, E. P. Donahue, and D. H. Wasserman
5-Aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside renders glucose output by the liver of the dog insensitive to a pharmacological increment in insulin
Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1039 - E1043.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2005 by the American Diabetes Association.