title: Dietary protein restriction decreases insulin-like growth factor I independent of insulin and liver growth hormone binding.
abstract: 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.
authors.affiliation: Unité de Diabétologie et Nutrition, School of Medicine, University of Louvain, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Maiter
authors.forename: T
authors.initials: T
authors.lastname: Fliesen
authors.forename: L E
authors.initials: LE
authors.lastname: Underwood
authors.forename: M
authors.initials: M
authors.lastname: Maes
authors.forename: G
authors.initials: G
authors.lastname: Gerard
authors.forename: M L
authors.initials: ML
authors.lastname: Davenport
authors.forename: J M
authors.initials: JM
authors.lastname: Ketelslegers
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D011488:Protein Deficiency / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013002:Somatomedins / Q000378:metabolism*; D013311:Streptozocin
chemical_list: D004044:Dietary Proteins; D007328:Insulin; D013002:Somatomedins; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone