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 Zhao, H. Articles by LeRoith, D. Search for Related Content PubMed PubMed Citation Articles by Zhao, H. Articles by LeRoith, D. Social Bookmarking                What's this?

Phloridzin Improves Hyperglycemia But Not Hepatic Insulin Resistance in a Transgenic Mouse Model of Type 2 Diabetes

¹ Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
² Mouse Metabolic Core Facility, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

The chronic hyperglycemia that occurs in type 2 diabetes may cause deterioration of ß-cell function and insulin resistance in peripheral tissues. Mice that express a dominant-negative IGF-1 receptor, specifically in skeletal muscle (MKR mice), exhibit severe insulin resistance, hyperinsulinemia, dyslipidemia, and hyper-glycemia. To determine the role of hyperglycemia in the worsening of the diabetes state in these animals, MKR mice were treated with phloridzin (PHZ), which inhibits intestinal glucose uptake and renal glucose reabsorption. Blood glucose levels were decreased and urine glucose levels were increased in response to PHZ treatment in MKR mice. PHZ treatment also increased food intake in MKR mice; however, the fat mass was decreased and lean body mass did not change. Serum insulin, fatty acid, and triglyceride levels were not affected by PHZ treatment in MKR mice. Hyperinsulinemic-euglycemic clamp analysis demonstrated that glucose uptake in white adipose tissue was significantly increased in response to PHZ treatment. Despite the reduction in blood glucose following PHZ treatment, there was no improvement in insulin-stimulated whole-body glucose uptake in MKR mice and neither was there suppression of endogenous glucose production by insulin. These results suggest that glucotoxicity plays little or no role in the worsening of insulin resistance that occurs in the MKR mouse model of type 2 diabetes.

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

This article has been cited by other articles:

				H. Ying, O. Araki, F. Furuya, Y. Kato, and S.-Y. Cheng Impaired Adipogenesis Caused by a Mutated Thyroid Hormone {alpha}1 Receptor Mol. Cell. Biol., March 15, 2007; 27(6): 2359 - 2371. [Abstract] [Full Text] [PDF]

				C.-H. Kim, P. Pennisi, H. Zhao, S. Yakar, J. B. Kaufman, K. Iganaki, J. Shiloach, P. E. Scherer, M. J. Quon, and D. LeRoith MKR mice are resistant to the metabolic actions of both insulin and adiponectin: discordance between insulin resistance and adiponectin responsiveness Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E298 - E305. [Abstract] [Full Text] [PDF]

				L. J. Murphy Insulin-like growth factor-I: a treatment for type 2 diabetes revisited. Endocrinology, June 1, 2006; 147(6): 2616 - 2618. [Full Text] [PDF]

				P. Pennisi, O. Gavrilova, J. Setser-Portas, W. Jou, S. Santopietro, D. Clemmons, S. Yakar, and D. LeRoith Recombinant Human Insulin-Like Growth Factor-I Treatment Inhibits Gluconeogenesis in a Transgenic Mouse Model of Type 2 Diabetes Mellitus Endocrinology, June 1, 2006; 147(6): 2619 - 2630. [Abstract] [Full Text] [PDF]

				Y. Toyoshima, O. Gavrilova, S. Yakar, W. Jou, S. Pack, Z. Asghar, M. B. Wheeler, and D. LeRoith Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes Endocrinology, September 1, 2005; 146(9): 4024 - 4035. [Abstract] [Full Text] [PDF]