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) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Kintscher, U. Articles by Law, R. E. Search for Related Content PubMed PubMed Citation Articles by Kintscher, U. Articles by Law, R. E.

INVITED REVIEW

PPAR-mediated insulin sensitization: the importance of fat versus muscle

¹Center for Cardiovascular Research, Institut für Pharmakologie und Toxikologie, Campus Charité-Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany; and ²Takeda Pharmaceuticals North America, Inc., Lincolnshire, Illinois

Peroxisome proliferator-activated receptor- (PPAR) is a nuclear hormone receptor that functions as a transcriptional regulator in a variety of tissues. PPAR activation, e.g., through binding of the synthetic glitazones or thiazolidinediones (TZD), results in a marked improvement in type 2 diabetic patients of insulin and glucose parameters resulting from an improvement of whole body insulin sensitivity. The role of different metabolic tissues (fat, skeletal muscle, liver) in mediating PPAR function in glucose and insulin homeostasis is still unclear. Recently, the function of PPAR in adipose tissue and skeletal muscle has been intensively characterized by using targeted deletion of PPAR in those tissues. In those studies, adipose PPAR has been identified as an essential mediator for the maintainance of whole body insulin sensitivity. Two major mechanisms have been described. 1) Adipose PPAR protects nonadipose tissue against excessive lipid overload and maintains normal organ function (liver, skeletal muscle); and 2) adipose PPAR guarantees a balanced and adequate production of secretion from adipose tissue of adipocytokines such as adiponectin and leptin, which are important mediators of insulin action in peripheral tissues. In contrast to studies in adipose-specific PPAR-deficient mice, the data in muscle-specific PPAR^–/– mice demonstrate that whole body insulin sensitivity is, at least in part, relying on an intact PPAR system in skeletal muscle. Finally, these early and elegant studies using tissue-specific PPAR knockout mouse models pinpoint adipose tissue as the major target of TZD-mediated improvement of hyperlipidemia and insulin sensitization.

peroxisome proliferator-activated receptor-; diabetes; glitazone

This article has been cited by other articles:

				K. Hojlund, D. Glintborg, N. R. Andersen, J. B. Birk, J. T. Treebak, C. Frosig, H. Beck-Nielsen, and J. F.P. Wojtaszewski Impaired Insulin-Stimulated Phosphorylation of Akt and AS160 in Skeletal Muscle of Women With Polycystic Ovary Syndrome Is Reversed by Pioglitazone Treatment Diabetes, February 1, 2008; 57(2): 357 - 366. [Abstract] [Full Text] [PDF]

				K. Kos, A. L. Harte, S. James, D. R. Snead, J. P. O'Hare, P. G. McTernan, and S. Kumar Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1335 - E1340. [Abstract] [Full Text] [PDF]

				W. Li, J. Tonelli, P. Kishore, R. Owen, E. Goodman, P. E. Scherer, and M. Hawkins Insulin-sensitizing effects of thiazolidinediones are not linked to adiponectin receptor expression in human fat or muscle Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1301 - E1307. [Abstract] [Full Text] [PDF]

				S. Savas, I. W. Taylor, J. L. Wrana, and H. Ozcelik Functional nonsynonymous single nucleotide polymorphisms from the TGF-{beta} protein interaction network Physiol Genomics, April 24, 2007; 29(2): 109 - 117. [Abstract] [Full Text] [PDF]

				H. Zhou, C. M. Evock-Clover, J. P. McMurtry, C. M. Ashwell, and S. J. Lamont Genome-Wide Linkage Analysis to Identify Chromosomal Regions Affecting Phenotypic Traits in the Chicken. IV. Metabolic Traits Poult. Sci., February 1, 2007; 86(2): 267 - 276. [Abstract] [Full Text] [PDF]

				G. K. Bandyopadhyay, J. G. Yu, J. Ofrecio, and J. M. Olefsky Increased Malonyl-CoA Levels in Muscle From Obese and Type 2 Diabetic Subjects Lead to Decreased Fatty Acid Oxidation and Increased Lipogenesis; Thiazolidinedione Treatment Reverses These Defects. Diabetes, August 1, 2006; 55(8): 2277 - 2285. [Abstract] [Full Text] [PDF]

				B. Desvergne, L. Michalik, and W. Wahli Transcriptional Regulation of Metabolism Physiol Rev, April 1, 2006; 86(2): 465 - 514. [Abstract] [Full Text] [PDF]