Submitted to: Endocrine Society Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2006
Publication Date: 6/24/2006
Citation: Oliver, W.T., Rosenberger, J., Lopez, R., Fiorotto, M.L. 2006. The local IGF-I enhances the sensitivity of muscle protein synthesis to insulin [abstract]. The 88th Annual Meeting of The Endocrine Society, June 24-27, 2006, Boston, Massachusetts. Abstract #OR40-6, p. 134. Interpretive Summary:
Technical Abstract: Skeletal muscle protein synthesis in the immature muscle is highly sensitive to insulin and nutrients. We hypothesized that the sensitivity is due to local IGFs expressed at a significant level by immature muscle. To test the hypothesis, 3-wk-old transgenic mice with high muscle-specific IGF-I expression (SIS2, n=23) and wildtype (Wt, n=24) controls were either fasted overnight, refed for 90 min, or refed+diazoxide-treated (DZX) (to block insulin secretion). Muscle fractional protein synthesis rate (FSR) was measured "in vivo" over the last 15 min using a flooding dose of 3[H]-phenylalanine (1.5 mmol phe/kg BW). Blood was collected to measure serum insulin and glucose. The quadriceps were recovered for analysis of 3[H]-phen incorporation, and the total abundance and degree of tyr phosphorylation of the type 1 IGF (IGF-1R) and insulin receptors (IR) by Western blot analysis. Results are summarized in the table. The feeding-induced increase in insulin was blocked by DZX and levels remained fasting concentrations. Glucose levels in the fasting and refed groups were similar, but increased by 2- to 4-fold in DZX-treated mice. Feeding increased the activation of the IGF-1R in all mice. Fasting IR phosphorylation was low, and genotype differences were not discernable; feeding activated the IR in both genotypes, but to a greater extent in SIS2 mice. IR phosphorylation was undetectable following DZX treatment. SIS2 mice maintained higher FSR than Wt mice with fasting. Refeeding increased FSR for both genotypes, but the DZX treatment inhibited the feeding- and IGF-I-induced stimulation of FSR. The higher FSR in fasted SIS2 mice and greater IR activation upon refeeding are consistent with the hypothesis that local IGF enhances the sensitivity of muscle protein synthesis to insulin. The response to DZX further shows that insulin is necessary for the response to IGF-I and that nutrients alone were insufficient to stimulate muscle protein FSR.