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) All Versions of this Article: 291/3/E491    most recent 00378.2005v1 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 (1) Citing Articles via Google Scholar Google Scholar Articles by Robertson, K. Articles by Liu, J.-L. Search for Related Content PubMed PubMed Citation Articles by Robertson, K. Articles by Liu, J.-L.

Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice

¹Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada; and ²Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio

Submitted 15 August 2005 ; accepted in final form 7 April 2006

Growth hormone (GH), acting through its receptor (GHR), is essential for somatic growth and development and maintaining metabolic homeostasis. GHR gene-deficient (GHR^–/–) mice exhibit drastically diminished insulin-like growth factor-I (IGF-I) levels, proportional growth retardation, elevated insulin sensitivity, and reduced islet -cell mass. Unlike the liver, which is mostly unaffected by changes in IGF-I level, skeletal muscles express high levels of IGF-I receptor (IGF-IR). The net result of a concurrent deficiency in the actions of both GH and IGF-I, which exert opposite influences on insulin responsiveness, has not been evaluated. We studied insulin-stimulated early responses in the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and p85 subunit of phosphatidylinositol 3-kinase. Upon in vivo insulin stimulation, skeletal muscles of GHR^–/– mice exhibit transient delayed responses in IR and IRS-1 phosphorylation but normal levels of p85 association with IRS-1. This is in contrast to normal/elevated insulin responses in hepatocytes and indicates tissue-specific effects of GHR gene deficiency. In addition to stimulating normal islet cell growth, GH may participate in islet cell overgrowth, which compensates for insulin resistance induced by obesity. To determine whether the islet cell overgrowth is dependent on GH signaling, we studied the response of male GHR^–/– mice to high-fat diet (HFD)-induced obesity. After 17 wk on a HFD, GHR^–/– mice became more significantly obese than wild-type mice and exhibited increased -cell mass to a slightly higher extent. These data demonstrate that GH signaling is not required for compensatory islet growth. Thus, in both muscle insulin responsiveness and islet growth compensation, normal levels of GH signals do not seem to play a dominant role.

gene-disrupted mice; insulin receptor; phosphorylation; -cell mass; high-fat diet

This article has been cited by other articles:

				J. S. Davies, E. F. Gevers, A. E. Stevenson, K. T. Coschigano, M. M. El-Kasti, M. J. Bull, C. Elford, B. A. J. Evans, J. J. Kopchick, and T. Wells Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1483 - E1494. [Abstract] [Full Text] [PDF]