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The Role of the Growth Hormone/Insulin-Like Growth Factor I Axis in Stimulation of Protein Synthesis in Skeletal Muscles Following Oral Refeeding

Department of Surgery and Internal Medicine
¹ , University of Göteborg, Sweden and Genentech, Inc., South San Francisco, California

Address all correspondence and requests for reprints to: Professor Kent Lundholm, Department of Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.

The mechanisms behind stimulation of protein synthesis in skeletal muscles following oral feeding are not well understood. Previous research has not confirmed that insulin is a major factor behind this stimulation. In the present study we have used genetically altered mice, with either a lack of GH secretion due to a mutational gene inactivation [GH (-/-) dwarf, DW/JOrlBom-dw] or mice with a homozygous site-specific insertion mutation in the insulin-like growth factor-1 gene [IGF-I (m/m)], leading to a deficient IGF-I production. These gene knock-outs were used in comparison to their normal wild types for evaluation of the role that the GH/IGF-I axis may have in activation of nutritionally induced stimulation of protein synthesis in skeletal muscles during oral refeeding. Weight stable adult C57Bl6 mice served as an additional normal control group. Protein synthesis was measured by a modified flooding dose technique with radioactive L-[¹⁴C-U]phenylalanine incorporation into acid precipitated muscle proteins.

Fractional protein synthesis in skeletal muscles after an overnight fast was comparable among C57Bl6 (0.076 ± 0.009%/h), wild-type IGF-I(+/+) (0.061 ± 0.008) and IGF-I(m/m) deficient mice (0.068 ± 0.006%/h), whereas GH(-/-) incompetent mice had a lower fractional synthesis rate compared with GH(+/+) competent mice (0.045 ± 0.006 vs. 0.068 ± 0.007, P < 0.05). Refeeding with standard chow diet stimulated protein synthesis in muscles by more than 60% in all animal groups. This response was independent of circulating GH, total IGF-I concentrations in blood, as well as up-regulation of locally produced IGF-I messenger RNA (mRNA) in skeletal muscles.

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