Short-term hypocaloric nutrition but not bed rest decrease insulin sensitivity and IGF-I bioavailability in healthy subjects: the importance of glucagon

Hyperinsulinemic, normoglycemic clamps were performed before and after 24 h of either hypocaloric nutrition or bed rest in healthy subjects. Decreased insulin sensitivity and insulin-like growth factor-I (IGF-I) bioavalibility, as measured by the serum IGF-I/insulin-like growth factor binding protein-1 (IGFBP-1) ratio, was found after fasting, whereas no metabolic changes were found after bed rest. Glucagon seems to be a key regulator of IGFBP-1 after brief hypocaloric nutrition. Hypocaloric nutrition and immobilization may add to the catabolic response to surgery and other trauma. Presently, six healthy subjects were studied before and after a 24-h period of hypocaloric nutrition (200 kcal/24 h, fast) or immobilization (bed rest) using the hyperinsulinemic (0.8 mU.kg-1.min-1), normoglycemic (4.5 mmol/L) clamp, indirect calorimetry, and circulating levels of substrates and hormones. After fast, body weight decreased (P < 0.05), and nitrogen balance was negative (-10 +/- 1 g urea nitrogen/24 h). Basal levels of free fatty acids, glucagon, and IGFBP-1 increased (P < 0.05), whereas c-peptide levels and the IGF-I/IGFBP-1 ratio decreased (P < 0.05). However, no change was found in basal levels of IGF-1 or substrate oxidation. Furthermore, changes (%) in basal levels of glucagon after fast correlated to IGFBP-1 (r = 1.0, P < 0.05), whereas the suppressibility of IGFBP-1 by insulin was maintained at normal levels. During clamps, glucose infusion rates (GIR) decreased after fast (-43 +/- 13%, mean +/- SEM, P < 0.001). Although not significantly, clamp levels of fat oxidation tended to increase and glucose oxidation tended to decrease. Levels of IGFBP-1 during clamps were higher as compared with the control clamp (P < 0.05). No adverse metabolic changes were seen after bed rest, and no change in GIR during clamps were seen as compared with the control measurement (0 +/- 14%). After brief hypocaloric nutrition, insulin sensitivity is reduced, whereas IGF-I bioavalibility is reduced by an increase in levels of IGFBP-1. Glucagon seems to contribute to the increase in IGFBP-1 during these conditions.