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 Thirone, A. C.P. Articles by Saad, M. J.A. Search for Related Content PubMed PubMed Citation Articles by Thirone, A. C.P. Articles by Saad, M. J.A. Social Bookmarking                What's this?

Modulation of Growth Hormone Signal Transduction in Kidneys of Streptozotocin-Induced Diabetic Animals

Effect of a Growth Hormone Receptor Antagonist

From the Department of Internal Medicine, FCM, University Of Campinas, Campinas, Sao Paulo, Brazil

Growth hormone (GH) and IGFs have a long distinguished history in diabetes, with possible participation in the development of renal complications. The implicated effect of GH in diabetic end-stage organ damage may be mediated by growth hormone receptor (GHR) or postreceptor events in GH signal transduction. The present study investigates the effects of diabetes induced by streptozotocin (STZ) on renal GH signaling. Our results demonstrate that JAK2, insulin receptor substrate (IRS)-1, Shc, ERKs, and Akt are widely distributed in the kidney, and after GH treatment, there is a significant increase in phosphorylation of these proteins in STZ-induced diabetic rats compared with controls. Moreover, the GH-induced association of IRS-1/phosphatidylinositol 3-kinase, IRS-1/growth factor receptor bound 2 (Grb2), and Shc/Grb2 are increased in diabetic rats as well. Immunohistochemical studies show that GH-induced p-Akt and p-ERK activation is apparently more pronounced in the kidneys of diabetic rats. Administration of G120K-PEG, a GH antagonist, in diabetic mice shows inhibitory effects on diabetic renal enlargement and reverses the alterations in GH signal transduction observed in diabetic animals. The present study demonstrates a role for GH signaling in the pathogenesis of early diabetic renal changes and suggests that specific GHR blockade may present a new concept in the treatment of diabetic kidney disease.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				X. Xin, S. Chen, Z. A. Khan, and S. Chakrabarti Akt activation and augmented fibronectin production in hyperhexosemia Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1036 - E1044. [Abstract] [Full Text] [PDF]

				R. Barbuio, M. Milanski, M. B Bertolo, M. J Saad, and L. A Velloso Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet J. Endocrinol., September 1, 2007; 194(3): 539 - 550. [Abstract] [Full Text] [PDF]

				G. R. Reddy, M. J. Pushpanathan, R. F. Ransom, L. B. Holzman, F. C. Brosius III, M. Diakonova, P. Mathieson, M. A. Saleem, E. O. List, J. J. Kopchick, et al. Identification of the Glomerular Podocyte as a Target for Growth Hormone Action Endocrinology, May 1, 2007; 148(5): 2045 - 2055. [Abstract] [Full Text] [PDF]

				J. Kaput, K. G. Klein, E. J. Reyes, W. A. Kibbe, C. A. Cooney, B. Jovanovic, W. J. Visek, and G. L. Wolff Identification of genes contributing to the obese yellow Avy phenotype: caloric restriction, genotype, diet x genotype interactions Physiol Genomics, August 11, 2004; 18(3): 316 - 324. [Abstract] [Full Text] [PDF]