| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Departments of Physiology (G.P., D.R.S., P.K.L.) and Pediatrics (C.R.F., A.J.D., P.K.L.), University of North Carolina, Chapel, North Carolina 27599-7545; AgResearch, Ruakura Research Center (J.M.O.), Hamilton, New Zealand Private Bag 3213; and the Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School (C.R.K.), Boston, Massachusetts 02215
Address all correspondence and requests for reprints to: Dr. Pauline Kay Lund, Ph.D., Department of Cell and Molecular Physiology, CB# 7545, University of North Carolina, Chapel Hill, North Carolina 27599-7545. E-mail empk{at}med.unc.edu
Organ weight was compared in adult mice with deletion of one (IRS-1-/+) or both (IRS-1-/-) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1+/+ littermates. IRS-1-/+ mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1-/- mice showed major reductions in weight of heart, liver, and spleen that were directly proportional to a decrease in body weight. In IRS-1-/- mice, kidney and particularly small intestine and brain exhibited proportionately smaller weight reductions, and gastrocnemius muscle showed a proportionately greater weight reduction than the decrease in body weight. Growth deficits in IRS-1-/- mice could reflect impaired actions of multiple hormones or cytokines that activate IRS-1. To assess the requirement for IRS-1 in insulin-like growth factor I (IGF-I)-dependent postnatal growth, IRS-1-/+ mice were cross-bred with mice that widely overexpress a human IGF-I transgene (IGF+) to generate IGF+ and wild-type mice on an IRS-1+/+, IRS-1-/+, and IRS-1-/- background. IGF-I overexpression increased body weight and weight of brain, small intestine, kidney, spleen, heart, and gastrocnemius muscle in IRS-1+/+ mice. IGF-I overexpression could not completely reverse the body growth retardation in IRS-1-/- mice. Absolute or partial IRS-1 deficiency impaired IGF-I-induced body overgrowth more in females than in males. In males and females, IGF-I stimulated similar overgrowth of brain regardless of IRS-1 status, and intestine and spleen showed dose dependence on IRS-1 for IGF-I-induced growth. IGF-I-induced growth of gastrocnemius muscle had an absolute requirement for IRS-1. IGF-I-induced growth of kidney and heart was impaired by IRS-1 deficiency only in females. In vivo, therefore, most organs do not require IRS-1 for IGF-I-induced growth and can use alternate signaling molecules to mediate IGF-I action. Other organs, such as gastrocnemius muscle, require IRS-1 for IGF-I-induced growth in vivo.
This article has been cited by other articles:
 |
|
 |
|
  J. K Liu and J. P Lynch The modulation of IGF-1 signalling by the intestine-specific factor CDX2 Gut, September 1, 2009; 58(9): 1179 - 1180. [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Ramocki, H. R. Wilkins, S. T. Magness, J. G. Simmons, B. P. Scull, G. H. Lee, K. K. McNaughton, and P. K. Lund Insulin Receptor Substrate-1 Deficiency Promotes Apoptosis in the Putative Intestinal Crypt Stem Cell Region, Limits Apcmin/+ Tumors, and Regulates Sox9 Endocrinology, January 1, 2008; 149(1): 261 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Shi, L. Sepp-Lorenzino, M. Prisco, P. Linsley, T. deAngelis, and R. Baserga Micro RNA 145 Targets the Insulin Receptor Substrate-1 and Inhibits the Growth of Colon Cancer Cells J. Biol. Chem., November 9, 2007; 282(45): 32582 - 32590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Simmons, Y. Ling, H. Wilkins, C. R. Fuller, A. J. D'Ercole, J. Fagin, and P. K. Lund Cell-specific effects of insulin receptor substrate-1 deficiency on normal and IGF-I-mediated colon growth Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G995 - G1003. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dalmizrak, A. Wu, J. Chen, H. Sun, F. E. Utama, D. Zambelli, T. H. Tran, H. Rui, and R. Baserga Insulin Receptor Substrate-1 Regulates the Transformed Phenotype of BT-20 Human Mammary Cancer Cells Cancer Res., March 1, 2007; 67(5): 2124 - 2130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, X. Tu, and R. Baserga A Mechanism for Cell Size Regulation by the Insulin and Insulin-Like Growth Factor-I Receptors Cancer Res., December 1, 2006; 66(23): 11106 - 11109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zheng, H. Yamada, K. Sakamoto, S. Horita, M. Kunimi, Y. Endo, Y. Li, K. Tobe, Y. Terauchi, T. Kadowaki, et al. Roles of Insulin Receptor Substrates in Insulin-Induced Stimulation of Renal Proximal Bicarbonate Absorption J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2288 - 2295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Wu, X. Tu, M. Prisco, and R. Baserga Regulation of Upstream Binding Factor 1 Activity by Insulin-like Growth Factor I Receptor Signaling J. Biol. Chem., January 28, 2005; 280(4): 2863 - 2872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Gagliardi, E. Y. W. Kuo, S. Raulic, G. F. Wagner, and G. E. DiMattia Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E92 - E105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Drakas, X. Tu, and R. Baserga Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase PNAS, June 22, 2004; 101(25): 9272 - 9276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Prisco, A. Maiorana, C. Guerzoni, G. Calin, B. Calabretta, R. Voit, I. Grummt, and R. Baserga Role of Pescadillo and Upstream Binding Factor in the Proliferation and Differentiation of Murine Myeloid Cells Mol. Cell. Biol., June 15, 2004; 24(12): 5421 - 5433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Broussard, R. H. McCusker, J. E. Novakofski, K. Strle, W. H. Shen, R. W. Johnson, R. Dantzer, and K. W. Kelley IL-1{beta} Impairs Insulin-Like Growth Factor I-Induced Differentiation and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts J. Immunol., June 15, 2004; 172(12): 7713 - 7720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Michael, S. Haq, X. Chen, E. Hsich, L. Cui, B. Walters, Z. Shao, K. Bhattacharya, H. Kilter, G. Huggins, et al. Glycogen Synthase Kinase-3{beta} Regulates Growth, Calcium Homeostasis, and Diastolic Function in the Heart J. Biol. Chem., May 14, 2004; 279(20): 21383 - 21393. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Broussard, R. H. MCCusker, J. E. Novakofski, K. Strle, W. Hong Shen, R. W. Johnson, G. G. Freund, R. Dantzer, and K. W. Kelley Cytokine-Hormone Interactions: Tumor Necrosis Factor {alpha} Impairs Biologic Activity and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts Endocrinology, July 1, 2003; 144(7): 2988 - 2996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Kulkarni, K. Almind, H. J. Goren, J. N. Winnay, K. Ueki, T. Okada, and C. R. Kahn Impact of Genetic Background on Development of Hyperinsulinemia and Diabetes in Insulin Receptor/Insulin Receptor Substrate-1 Double Heterozygous Mice Diabetes, June 1, 2003; 52(6): 1528 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sun, X. Tu, M. Prisco, A. Wu, I. Casiburi, and R. Baserga Insulin-Like Growth Factor I Receptor Signaling and Nuclear Translocation of Insulin Receptor Substrates 1 and 2 Mol. Endocrinol., March 1, 2003; 17(3): 472 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Tu, P. Batta, N. Innocent, M. Prisco, I. Casaburi, B. Belletti, and R. Baserga Nuclear Translocation of Insulin Receptor Substrate-1 by Oncogenes And Igf-I. EFFECT ON RIBOSOMAL RNA SYNTHESIS* J. Biol. Chem., November 8, 2002; 277(46): 44357 - 44365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. White IRS proteins and the common path to diabetes Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E413 - E422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Prisco, F. Santini, R. Baffa, M. Liu, R. Drakas, A. Wu, and R. Baserga Nuclear Translocation of Insulin Receptor Substrate-1 by the Simian Virus 40 T Antigen and the Activated Type 1 Insulin-like Growth Factor Receptor J. Biol. Chem., August 23, 2002; 277(35): 32078 - 32085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. SESTI, M. FEDERICI, M. L. HRIBAL, D. LAURO, P. SBRACCIA, and R. LAURO Defects of the insulin receptor substrate (IRS) system in human metabolic disorders FASEB J, October 1, 2001; 15(12): 2099 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Flier, R. N. Kulkarni, and C. R. Kahn Evidence for a circulating islet cell growth factor in insulin-resistant states PNAS, June 7, 2001; (2001) 131192998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Flier, R. N. Kulkarni, and C. R. Kahn Evidence for a circulating islet cell growth factor in insulin-resistant states PNAS, June 19, 2001; 98(13): 7475 - 7480. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
