Nutritional modulation of canine insulin-like growth factors and their binding proteins A Maxwell, R Butterwick 1 , M Yateman, R M Batt 2 , A Cotterill and C Camacho-Hu¨bner Departments of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK, 1 WALTHAM Centre for Pet Nutrition, Waltham-on-the-Wolds, Leicestershire, UK and 2 Department of Small Animal Medicine and Surgery, Royal Veterinary College, University of London, London, UK (Requests for offprints should be addressed to C Camacho-Hu¨bner, Department of Chemical Endocrinology, St Bartholomew’s Hospital, 51–53 Bartholomew Close, London EC1A 7BE, UK) Abstract The response of canine insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) to moderate nutri- tional restriction followed by refeeding has not previously been studied in detail. The purpose of these studies was to examine the effects of nutritional restriction on the IGF system of adult dogs. Normal serum IGF values were established after validation of heterologous RIAs for measuring canine IGFs-I and -II. Canine serum IGFBP profiles were examined by Western ligand blotting (WLB), using radiolabelled recombinant human (rh) IGF-I as the ligand, and were found to be similar to those of other species. IGF-I and IGFBP-3 concentrations correlated with body weight, thus reflecting breed size as previously shown, whereas IGF-II concentrations did not. IGFBP-2 serum concentrations and band intensity on WLB were increased compared with normal human serum IGFBP-2. Overnight fasting had no effect on IGF or IGFBP concentrations, including IGFBP-1, nor did refeeding. Prolonged restriction to 56% and then 42·5% of maintenance energy requirements for 2 weeks decreased IGF-I concentrations by 20·4% and 32·7% respectively. Feeding of the same diet ad libitum for 2 weeks normalised IGF-I concentrations. There were no changes in IGF-II or insulin levels. Serum IGFBP-2 concentrations increased with 56% restriction of maintenance energy (P=0·03). We conclude that serum IGF-I is potentially a useful marker of short-term change in nutritional status in the adult dog. Journal of Endocrinology (1998) 158, 77–85 Introduction Studies of the role of nutrition in modulation of the growth hormone (GH)–insulin-like growth factor (IGF) axis have been carried out mainly in omnivores and herbivores. Certain aspects of glucose and carbohydrate metabolism in carnivores differ from those in animals taking omnivorous or herbivorous diets, particularly in the fasted state. Hepatic gluconeogenic activity is higher in carnivores and does not increase with fasting (Kettlehut et al. 1980). Insulin sensitivity and glucose tolerance are decreased in animals eating high protein diets compared with those eating carbohydrate-rich diets (Belo et al. 1976, Kettlehut et al. 1980). Circulating somatomedin-like activity was reported by Van den Brande et al. (1974), who used canine plasma in human and rat cartilage bioassay models. This study suggested that the growth-promoting actions of this canine growth factor were similar to those in other species. Furthermore, Eigenmann et al. (1985) demonstrated that the dog showed changes in serum IGF-I in response to change in nutritional status that were similar to those in other species. Serum IGF-I concentrations decreased significantly after a 19 day fast, then increased rapidly to normal values with 9 days of refeeding. The influence of nutrition on serum IGFs and IGF binding proteins (IGFBPs) has been demonstrated in many species. Fasting progressively reduces serum IGF-I con- centrations in man (Clemmons et al. 1981) and in rats (Emler & Schalch 1987, Goldstein et al. 1991), which reflects changes in hepatic IGF-I mRNA. Fasting, either overnight or longer, results in a significant increase in IGFBP-1 concentrations in man (Busby et al. 1988, Cotterill et al. 1993) and rat (Rivero et al. 1995), which decline with feeding. In neonatal rats, this coincided with changes in hepatic mRNA expression. Other IGFBPs require a longer or more severe nutritional challenge before they are affected. A fast of 48 h was necessary to increase rat IGFBP-2 concentrations (Orlowski et al. 1990), whereas IGFBP-2 concentrations in obese human volunteers increased significantly only after 9 days of fasting (Clemmons et al. 1991). Restriction of dietary components, energy and protein, also affects the IGF/ IGFBP system, resulting in decreased serum IGF-I and 77 Journal of Endocrinology (1998) 158, 77–85 ? 1998 Society for Endocrinology Printed in Great Britain 0022–0795/98/0158–0077 $08.00/0 Downloaded from Bioscientifica.com at 02/10/2023 02:51:16PM via free access