This Article Full Text Full Text (PDF) All Versions of this Article: 147/12/5760    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart 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 PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Irwin, R. Articles by McCabe, L. R. Search for Related Content PubMed PubMed Citation Articles by Irwin, R. Articles by McCabe, L. R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH

Normal Bone Density Obtained in the Absence of Insulin Receptor Expression in Bone

Departments of Physiology and Radiology and Biomedical Imaging Research Center (R.I., K.J.M., L.R.M.), Michigan State University, East Lansing, Michigan 48824; and Department of Medicine (H.V.L.), Columbia University, New York, New York

Address all correspondence and requests for reprints to: Laura R. McCabe, Ph.D., Michigan State University, Departments of Physiology and Radiology, 2201 Biomedical Physical Science Building, East Lansing, Michigan 48824. E-mail: mccabel{at}msu.edu.

Type I diabetes is characterized by little or no insulin production and hyperglycemic conditions. It is also associated with significant bone loss and increased bone marrow adiposity. To examine the role of reduced insulin signaling in type I diabetic bone loss without inducing hyperglycemia, we used genetically reconstituted insulin receptor knockout mice (IRKO-L1) that are euglycemic as a result of human insulin receptor transgene expression in the pancreas, liver, and brain. RT-PCR analyses demonstrated undetectable levels of insulin receptor expression in IRKO-L1 bone, yet IRKO-L1 bones exhibit similar (and trend toward greater) bone density compared with wild-type animals as determined by microcomputed tomography. More detailed bone analyses indicated that cortical bone area was increased in tibias of IRKO-L1 mice. Osteoblast markers (osteocalcin and runx2 mRNA levels) and resorption markers (serum pyridinoline levels) were similar in wild-type and IRKO-L1 bones. When marrow adiposity was examined, we noticed a decrease in adipocyte number and fatty-acid-binding protein 2 expression in IRKO-L1 mice compared with wild-type mice. Bone marrow stromal cell cultures obtained from wild-type and IRKO-L1 mice demonstrated similar adipogenic and osteogenic potentials, indicating that systemic factors likely contribute to differences in marrow adiposity in vivo. Interestingly, IGF-I receptor mRNA levels were elevated in IRKO-L1 bones, suggesting (in combination with hyperinsulinemic conditions) that increased IGF-I receptor signaling may represent a compensatory response and contribute to the changes in cortical bone. Taken together, these results suggest that reduced insulin receptor signaling in bone is not a major factor contributing to bone loss in type I diabetes.

This article has been cited by other articles:

				K. Fulzele, D. J. DiGirolamo, Z. Liu, J. Xu, J. L. Messina, and T. L. Clemens Disruption of the Insulin-like Growth Factor Type 1 Receptor in Osteoblasts Enhances Insulin Signaling and Action J. Biol. Chem., August 31, 2007; 282(35): 25649 - 25658. [Abstract] [Full Text] [PDF]

				M. Misra, K. K. Miller, J. Cord, R. Prabhakaran, D. B. Herzog, M. Goldstein, D. K. Katzman, and A. Klibanski Relationships between Serum Adipokines, Insulin Levels, and Bone Density in Girls with Anorexia Nervosa J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2046 - 2052. [Abstract] [Full Text] [PDF]