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This Article Full Text Full Text (PDF) All Versions of this Article: 289/2/E288    most recent 00494.2004v1 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 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 Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Tang, Z. Articles by Liu, J.-L. Search for Related Content PubMed PubMed Citation Articles by Tang, Z. Articles by Liu, J.-L.

Age-dependent onset of liver-specific IGF-I gene deficiency and its persistence in old age: implications for postnatal growth and insulin resistance in LID mice

¹Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada; ²Endocrine and Metabolic Division, E-Institutes of Shanghai Universities, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai, China; and ³National Hormone and Peptide Program, Harbor-University of California Los Angeles Medical Center, Torrance, California

Submitted 19 October 2004 ; accepted in final form 10 March 2005

To explore the limitations of the liver-specific IGF-I gene-deficient (LID) model and to further evaluate the role of endocrine IGF-I in early postnatal life and old age, we have studied these mice during the prepubertal period (from birth to 3 wk of age) and when they are 2 yr old. During the first 2 wk of life, IGF-I gene deficiency and the resulting reduction in serum IGF-I levels in LID mice did not reach sufficiently low levels when mice experience the most rapid and growth hormone (GH)-independent growth. It suggests that the role of liver-derived IGF-I in prepubertal, GH-independent postnatal growth cannot be established. From our previous studies, liver IGF-I mRNA level was abolished in adult LID mice, which causes elevated GH level, insulin resistance, pancreatic islet enlargement, and hyperinsulinemia. Interestingly in 2-yr-old LID mice, although liver IGF-I mRNA and serum IGF-I levels were still suppressed, serum insulin and GH levels had returned to normal. Compared with same-sex control littermates, aged male LID mice had significantly reduced body weight and fat mass and exhibited normal insulin sensitivity. On the other hand, aged female LID mice exhibited normal weight and marginal resistance to insulin actions. The pancreatic islet percentage (reflecting islet cell mass) was also restored to normal levels in aged LID mice. Thus, although the IGF-I gene deficiency is well maintained into old age, the insulin sensitivity, islet enlargement, and hyperinsulinemia that occurred in young adult mice have been mostly restored to normal levels, further supporting the age-dependent and sexual dimorphic features of the LID mice.

Cre recombinase; sexual dimorphism; pancreatic islets; insulin-like growth factor I; liver-specific insulin-like growth factor I gene deficiency

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