Endocrinology, Vol 124, 2604-2611, Copyright © 1989 by Endocrine Society

ARTICLES

Dietary protein restriction decreases insulin-like growth factor I independent of insulin and liver growth hormone binding

D Maiter, T Fliesen, LE Underwood, M Maes, G Gerard, ML Davenport and JM Ketelslegers
Unite de Diabetologie et Nutrition, School of Medicine, University of Louvain, Brussels, Belgium.

To determine the role of hypoinsulinemia and liver somatogenic (GH) receptors in growth retardation and decreased serum insulin-like growth factor I (IGF-I) levels during protein restriction, we have used a rat model where the effects of a low protein intake on body weight (BW), serum IGF-I concentration, and liver GH binding could be evaluated in the presence of low or high insulin concentrations. Two days after being made diabetic with streptozotocin (60 mg/kg BW), 6-week-old female rats (nine per group) were begun on a low (5%) or normal (15%) protein diet, without or with insulin supplementation (3 U lente daily). Nondiabetic rats fed both diets were used as controls (nine per group). In the nondiabetic animals, 7 days of protein restriction reduced BW gain by 50% (P less than 0.001), serum insulin by 44% (P less than 0.025), and serum IGF-I concentrations by 28% (P less than 0.001) without significantly changing liver GH binding. By day 9, BW was decreased in the diabetic animals by 12%, serum insulin by 80%, serum IGF-I by 55%, and liver GH binding by 62%; these effects were similar in the 5% and 15% protein-fed rats (P less than 0.001 vs. the corresponding controls). In the diabetes fed the normal diet, insulin treatment restored BW gain, serum IGF-I, and liver GH binding to normal values. In contrast, in the diabetics fed a protein-restricted diet and treated with insulin, BW gain and serum IGF-I concentrations remained low, similar to those in the malnourished controls. This diet-induced growth attenuation was observed despite high circulating insulin (2-3 times normal values), appropriate glucose control (63 +/- 9 mg/dl), and near restoration of liver GH binding. We conclude that while both protein restriction and diabetes attenuate growth and reduce IGF-I concentrations, the effects of protein restriction are independent of the effects of insulin and probably act by alteration of postreceptor mechanisms.

This article has been cited by other articles:

				S. Grinspoon, K. K. Miller, D. B. Herzog, K. A. Grieco, and A. Klibanski Effects of Estrogen and Recombinant Human Insulin-Like Growth Factor-I on Ghrelin Secretion in Severe Undernutrition J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3988 - 3993. [Abstract] [Full Text] [PDF]

				S. Bourrin, P. Ammann, J. P. Bonjour, and R. Rizzoli Dietary Protein Restriction Lowers Plasma Insulin-Like Growth Factor I (IGF-I), Impairs Cortical Bone Formation, and Induces Osteoblastic Resistance to IGF-I in Adult Female Rats Endocrinology, September 1, 2000; 141(9): 3149 - 3155. [Abstract] [Full Text] [PDF]

				V. Beauloye, S. M. Muaku, P. Lause, D. Portetelle, R. Renaville, A. R. Robert, J. M. Ketelslegers, and D. Maiter Monoclonal antibodies to growth hormone (GH) prolong liver GH binding and GH-induced IGF-I/IGFBP-3 synthesis Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E308 - E315. [Abstract] [Full Text] [PDF]

				C. Veyrat-Durebex, P. Gaudreau, V. Coxam, N. Gaumet, and J. Alliot Peripheral injection of growth hormone stimulates protein intake in aged male and female Lou rats Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1105 - E1111. [Abstract] [Full Text] [PDF]

				S. Grinspoon, C. Corcoran, T. Stanley, L. Katznelson, and A. Klibanski Effects of Androgen Administration on the Growth Hormone-Insulin-Like Growth Factor I Axis in Men with Acquired Immunodeficiency Syndrome Wasting J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4251 - 4256. [Abstract] [Full Text]

				N. N. Kok, L. M. Morgan, C. M. Williams, M. B. Roberfroid, J.-P. Thissen, and N. M. Delzenne Insulin, Glucagon-like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Insulin-Like Growth Factor I as Putative Mediators of the Hypolipidemic Effect of Oligofructose in Rats J. Nutr., July 1, 1998; 128(7): 1099 - 1103. [Abstract] [Full Text] [PDF]

				C. Heinrichs, M. Colli, J. A. Yanovski, L. Laue, N. A. Gerstl, A. D. Kramer, J. A. Uyeda, and J. Baron Effects of Fasting on the Growth Plate: Systemic and Local Mechanisms Endocrinology, December 1, 1997; 138(12): 5359 - 5365. [Abstract] [Full Text] [PDF]

				S. Combes, I. Louveau, and M. Bonneau Moderate Food Restriction Affects Skeletal Muscle and Liver Growth Hormone Receptors Differently in Pigs J. Nutr., October 1, 1997; 127(10): 1944 - 1949. [Abstract] [Full Text]