HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Haluzik, M. Articles by LeRoith, D. Search for Related Content PubMed PubMed Citation Articles by Haluzik, M. Articles by LeRoith, D. Social Bookmarking                What's this?

Insulin Resistance in the Liver-Specific IGF-1 Gene-Deleted Mouse Is Abrogated by Deletion of the Acid-Labile Subunit of the IGF-Binding Protein-3 Complex

Relative Roles of Growth Hormone and IGF-1 in Insulin Resistance

¹ Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
² Department of Medicine, 1 Faculty of Medicine, Prague, Czech Republic
³ Department of Animal Science, Cornell University, Ithaca, New York

Liver IGF-1 deficient (LID) mice demonstrate a 75% reduction in circulating IGF-1 levels and a corresponding fourfold increase in growth hormone (GH) levels. At 16 weeks of age, LID mice demonstrate, using the hyperinsulinemic-euglycemic clamp, insulin insensitivity in muscle, liver, and fat tissues. In contrast, mice with a gene deletion of the acid-labile subunit (ALSKO) demonstrate a 65% reduction in circulating IGF-1 levels, with normal GH levels and no signs of insulin resistance. To further clarify the relative roles of increased GH and decreased IGF-1 levels in the development of insulin resistance, we crossed the two mouse lines and created a double knockout mouse (LID+ALSKO). LID+ALSKO mice demonstrate a further reduction in circulating IGF-1 levels (85%) and a concomitant 10-fold increase in GH levels. Insulin tolerance tests showed an improvement in insulin responsiveness in the LID+ALSKO mice compared with controls; LID mice were very insulin insensitive. Surprisingly, insulin sensitivity, while improved in white adipose tissue and in muscle, was unchanged in the liver. The lack of improvement in liver insulin sensitivity may reflect the absence of IGF-1 receptors or increased triglyceride levels in the liver. The present study suggests that whereas GH plays a major role in inducing insulin resistance, IGF-1 may have a direct modulatory role.

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

This article has been cited by other articles:

				Q.-s. Ji, M. J. Mulvihill, M. Rosenfeld-Franklin, A. Cooke, L. Feng, G. Mak, M. O'Connor, Y. Yao, C. Pirritt, E. Buck, et al. A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I receptor dependent tumor growth in vivo Mol. Cancer Ther., August 1, 2007; 6(8): 2158 - 2167. [Abstract] [Full Text] [PDF]

				O. M. Vidal, R. Merino, E. Rico-Bautista, L. Fernandez-Perez, D. J. Chia, J. Woelfle, M. Ono, B. Lenhard, G. Norstedt, P. Rotwein, et al. In Vivo Transcript Profiling and Phylogenetic Analysis Identifies Suppressor of Cytokine Signaling 2 as a Direct Signal Transducer and Activator of Transcription 5b Target in Liver Mol. Endocrinol., January 1, 2007; 21(1): 293 - 311. [Abstract] [Full Text] [PDF]

				V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]

				N. J. WILES, T. J. PETERS, D. A. LEON, and G. LEWIS Birth weight and psychological distress at age 45-51 years: Results from the Aberdeen Children of the 1950s cohort study The British Journal of Psychiatry, July 1, 2005; 187(1): 21 - 28. [Abstract] [Full Text] [PDF]

				Y. Lu, P. L. Herrera, Y. Guo, D. Sun, Z. Tang, D. LeRoith, and J.-L. Liu Pancreatic-Specific Inactivation of IGF-I Gene Causes Enlarged Pancreatic Islets and Significant Resistance to Diabetes Diabetes, December 1, 2004; 53(12): 3131 - 3141. [Abstract] [Full Text] [PDF]

				H. Zhao, S. Yakar, O. Gavrilova, H. Sun, Y. Zhang, H. Kim, J. Setser, W. Jou, and D. LeRoith Phloridzin Improves Hyperglycemia But Not Hepatic Insulin Resistance in a Transgenic Mouse Model of Type 2 Diabetes Diabetes, November 1, 2004; 53(11): 2901 - 2909. [Abstract] [Full Text] [PDF]

				P. A. Pennisi, J. J. Kopchick, S. Thorgeirsson, D. LeRoith, and S. Yakar Role of Growth Hormone (GH) in Liver Regeneration Endocrinology, October 1, 2004; 145(10): 4748 - 4755. [Abstract] [Full Text] [PDF]

				M. Haluzik, O. Gavrilova, and D. LeRoith Peroxisome Proliferator-Activated Receptor-{alpha} Deficiency Does Not Alter Insulin Sensitivity in Mice Maintained on Regular or High-Fat Diet: Hyperinsulinemic-Euglycemic Clamp Studies Endocrinology, April 1, 2004; 145(4): 1662 - 1667. [Abstract] [Full Text] [PDF]