Differential responses of IGF-I molecular complexes to military operational field training

Abstract

. Differential responses of IGF-I molecular complexes to military operational field training. J Appl Physiol 95: 1083-1089, 2003; 10.1152/japplphysiol. 01148.2002.-Insulin-like growth factor (IGF) I and IGF binding proteins (IGFBPs) modulate metabolic activity and tissue repair and are influenced by nutritional status. IGF-I circulates in free, ternary [IGF-I ϩ IGFBP-3 ϩ acid labile subunit (ALS)], and binary (IGF-I ϩ IGFBP) molecular complexes, and the relative proportions regulate IGF-I extravascular shifting and bioavailability. This study examined the hypothesis that sustained physical activity and sleep deprivation superimposed on a short-term energy deficit would alter the IGFBP concentrations and alter the proportions of IGF-I circulating in ternary vs. binary molecular complexes. Components of the IGF-I system (total and free IGF-I; IGFBP-1, -3, and ALS; nonternary IGF-I and IGFBP-3), biomarkers of metabolic and nutritional status (transferrin, ferritin, prealbumin, glucose, free fatty acids, glycerol, ␤-hydroxybutyrate), and body composition were measured in 12 men (22 Ϯ 3 yr, 87 Ϯ 8 kg, 183 Ϯ 7 cm, 20 Ϯ 5% body fat) on days 1, 3, and 4 during a control and experimental (Exp) period. During Exp, subjects performed prolonged work (energy expenditure of ϳ4,500 kcal/day) with caloric (1,600 kcal/day) and sleep (6.2 h total) restriction. IGF-I and IGFBP-3 were measured by immunoassay before and after immunoaffinity depletion of ALS-based complexes (i.e., ternary complex removal). Exp produced losses in body mass (Ϫ3.0%), lowered total IGF-I (Ϫ24%), free IGF-I (Ϫ42%), IGFBP-3 (Ϫ6%), nonternary IGF-I (Ϫ27%), and IGFBP-3 (Ϫ16%), and increased IGFBP-1 (256%). No Exp effects were observed for ALS. No changes were observed in the proportion of IGF-I circulating in free (ϳ1.2%), ternary (ϳ87.4%), or nonternary (ϳ11.4%) molecular complexes. During Exp, glucose concentrations were lower on day 3, but days 1 and 4 were statistically similar. In conclusion, during a short-term energy deficit in young, healthy men, 1) IGF-I system components differentially respond (both in direction and magnitude) to a given metabolic perturbation and 2) the relative proportion of IGF-I sequestered in ternary vs. nonternary molecular complexes appears to be well maintained.

Serum Sex Hormone–Binding Globulin and Cortisol Concentrations are Associated With Overreaching During Strenuous Military Training

“…A decrease in IGF-1 is suggested to indicate a diminished capacity for protein deposition. In addition, IGF-1 is sensitive to both energy intake and dietary protein content, and demonstrates significant decreases with inadequate dietary intake (23,24). Furthermore, a 7 week intensive endurance overload training program (36) and combined endurance and strength overload training for 6 weeks (5) have been found to decrease testosterone/cortisol ratios.…”

Utility of Measuring Insulin-Like Growth Factor-I for Assessing Military Operational Stress: Supporting Future Force Warrior from the Bench Top to the Battlefield

“…The physiological strain produced by these operational stressors can have deleterious effects on muscle mass, endocrine and metabolic function, as well as physical and mental performance (Friedl et al, 1994;Friedl, 1999;Friedl et al, 2000;Nindl et al, 1997;Nindl et al, 2002;Nindl et al, 2003a;Nindl et al, 2003b) (see Figure 1). A goal of the Army Medical Research and Materiel Command's (MRMC) biomedical research program is to identify useful biomarkers that are indicative of nutritional and physiological status that can be assessed rapidly, with minimally or non-invasive collection methods.…”

“…The growth hormone/insulin-like axis is a central endocrine axis and is thought to mediate many of the somatotrophic changes that are observed when warfighters are exposed to harsh field environments (Florini et al, 1996;Friedl et al, 2000;Nindl et al 2003a;Rosen, 1999;Rosendal et al, 2002). For this reason, periodic assessment of the growth hormone/insulin-like growth factor axis may have utility for sustaining warfighter health and performance.…”

“…The appeal of IGF-I as a biomarker is the dynamic nature in which circulating concentrations respond to nutritional stress. Underfeeding and proteincalorie malnutrition result in substantial reductions in IGF-I concentrations and the response persists until the nutritional stress is removed (Friedl et al, 2000;Frystyk et al, 1999;Nindl et al, 2003a;Rand et al, 2003;Thissen et al, 1992;Thissen et al, 1999). Additionally, IGF-I concentrations are relatively stable.…”

“…To study the acute responses to energy restriction we recently measured the circulating IGF-I and IGF binding proteins pattern of response to 4 days of near-continuous physical work, energy restriction, and sleep disruption (Nindl et al, 2003a). The participants had morning fasted blood drawn on days 1, 3, and 4 during a control week that contained physical performance testing, but no sustained physical activity, caloric restriction or sleep deprivation.…”