Journal of Clinical Endocrinology & Metabolism, Vol 81, 2474-2480, Copyright © 1996 by Endocrine Society

ARTICLES

Regulation of the insulin-like growth factor system by insulin in burn patients

CH Lang, J Fan, RA Frost, MC Gelato, Y Sakurai, DN Herndon and RR Wolfe
Department of Surgery, State University of New York, Stony Brook 11794, USA. LANG@SURG.SOM.SUNYSB.EDU

The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (approximately 60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral diet plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was 2.4 micrograms/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3-fold during the insulin period. No A-V difference across the leg was detected for IGFBP- 1, -2, or -3 in burn patients. In conclusion, burn injury in humans produces dramatic and sustained alterations in various components of the IGF system that persist despite adequate nutritional support. Our data indicate the presence of a net uptake of IGF-I by the leg in burn patients that may serve to counteract the catabolic state.

This article has been cited by other articles:

				C. H. Lang, D. Huber, and R. A. Frost Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R328 - R336. [Abstract] [Full Text] [PDF]

				C. H. Lang, T. C. Vary, and R. A. Frost Acute in Vivo Elevation of Insulin-Like Growth Factor (IGF) Binding Protein-1 Decreases Plasma Free IGF-I and Muscle Protein Synthesis Endocrinology, September 1, 2003; 144(9): 3922 - 3933. [Abstract] [Full Text] [PDF]

				C. H. Lang, G. J. Nystrom, and R. A. Frost Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R207 - R215. [Abstract] [Full Text] [PDF]

				B. Argüelles, V. Barrios, J. Pozo, M. T. Muñoz, and J. Argente Modifications of Growth Velocity and the Insulin-Like Growth Factor System in Children with Acute Lymphoblastic Leukemia: A Longitudinal Study J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4087 - 4092. [Abstract] [Full Text]

				E. Svanberg, R. A. Frost, C. H. Lang, J. Isgaard, L. S. Jefferson, S. R. Kimball, and T. C. Vary IGF-I/IGFBP-3 binary complex modulates sepsis-induced inhibition of protein synthesis in skeletal muscle Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1145 - E1158. [Abstract] [Full Text] [PDF]

				C. H. Lang, X. Liu, G. J. Nystrom, and R. A. Frost Acute response of IGF-I and IGF binding proteins induced by thermal injury Am J Physiol Endocrinol Metab, June 1, 2000; 278(6): E1087 - E1096. [Abstract] [Full Text] [PDF]

				R. A. Frost and C. H. Lang Differential Effects of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-1 on Protein Metabolism in Human Skeletal Muscle Cells Endocrinology, September 1, 1999; 140(9): 3962 - 3970. [Abstract] [Full Text]

				R. A. Frost, C. H. Lang, and M. C. Gelato Transient Exposure of Human Myoblasts to Tumor Necrosis Factor-{alpha} Inhibits Serum and Insulin-Like Growth Factor-I Stimulated Protein Synthesis Endocrinology, October 1, 1997; 138(10): 4153 - 4159. [Abstract] [Full Text] [PDF]

				B. L. G. Nyomba, L. Berard, and L. J. Murphy Free Insulin-Like Growth Factor I (IGF-I) in Healthy Subjects: Relationship with IGF-Binding Proteins and Insulin Sensitivity J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2177 - 2181. [Abstract] [Full Text] [PDF]