Modulation by dietary restriction in gene expression related to insulin-like growth factor-1 in rat muscle

Abstract

Physiological adaptations induced by dietary restriction might include the modulation of the insulin-like growth factor 1 (IGF-1) axis. We investigated the effects of dietary restriction on aging-dependent changes in plasma level of IGF-1 and gene expression levels of type-1 IGF receptor (IGFR), insulin receptor substrate-1 (IRS-1), and IGF-1 in the diaphragm and quadriceps femoris muscle (QFM) of male F344 rats. The animals were fed ad libitum throughout life (AL), or provided with 70% of diet of AL rats from 6 weeks of age (DR). The plasma IGF-1 and steady-state levels of the genes were quantified by radioimmunoassay and the reverse transcription-polymerase chain reaction method, respectively. Immunohistochemical analysis in tissue sections was also performed for IGFR. Our results showed that dietary restriction: 1) decreased the plasma level of IGF-1; 2) increased the steady-state level of IGFR-mRNA at 6 and 16 months of age. and the peptide level at 6 months; 3) maintained IGF-1- and IRS-1-mRNA at a level similar to that in AL rats; and 4) delayed or inhibited an aging-dependent increase in IGFR-mRNA in the muscles. The present results suggest that dietary restriction could modulate IGF-1 signaling by augmenting local tissue response to IGF-1 and by maintaining the local production of the peptide, even though plasma IGF-1 is reduced.