Changes in the circulating IGF system during short-term fasting and refeeding in rats

There is little information on free insulin-like growth factor I (IGF-I) and its regulatory proteins during fasting and refeeding. Therefore, we examined rats during fasting (0, 1, 2, and 3 days) and refeeding (3, 6, and 12 h and 1, 2, 3, and 7 days) (n = 6-9). Serum was analyzed for insulin, C-peptide, growth hormone (CH), free and total IGF-I, IGF-binding protein (IGFBP)-1 and -3, and the acid-labile subunit (ALS). Additionally, liver mRNA for IGF-I, IGFBP-1, and ALS was determined. Fasting reduced serum levels of GH, free and total IGF-I, IGFBP-3, and ALS, whereas IGFBP-1 was increased (P < 0.0001). Refeeding normalized IGFBP-1 at 3 h and GH at 12 h. Free IGF-I changed in parallel with total IGF-I, ALS, and IGFBP-3, being normalized at 48 h of refeeding. IGFBP-1 (peptide and mRNA) correlated inversely with insulin and C-peptide (P < 0.001). The correlation between peptide and mRNA was relatively strong for IGFBP-1 (r(2) = 0.36; P < 0.0001), moderate for IGF-I (r(2) = 0.18; P < 0.0005), and insignificant for ALS. In conclusion, insulin appears to regulate IGFBP-1 in fasted and refed rats. However, the normal inverse relationship between free IGF-I and IGFBP-1 was absent, and free IGF-I changed in parallel with total IGF-I and thus ALS and IGFBP-3. Finally, the regulation of the hepatic synthesis of IG F-I, IGFBP-1, and ALS seems to differ substantially.