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.
Nygren
J
J
Department of Surgery, Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
Thorell
A
A
Brismar
K
K
Karpe
F
F
Ljungqvist
O
O
D000328:Adult; D001510:Bed Rest / Q000009:adverse effects*; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D002153:Calorimetry, Indirect; D015331:Cohort Studies; D005215:Fasting / Q000009:adverse effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood* / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D005934:Glucagon; D005947:Glucose; D005990:Glycerol; D006854:Hydrocortisone