Effects of undernutrition and diabetes on serum and liver mRNA expression of IGFs and their binding proteins during rat development

Abstract

The purpose of the present study was to investigate the influence of nutrients and insulin on IGFs and their binding proteins (IGFBPs) during the fetal and neonatal periods of three rat populations: (a) rats undernourished by a 35% reduction in the diet from day 16 of gestation, (b) streptozotocin-induced diabetic rats from the same day, or 4 days after birth, and (c) control rats. Fetuses from the diabetic population showed a decrease in insulinemia at 19 and 21 days, along with an increase in glycemia at all stages. Neither glycemia nor insulinemia changed in the fetuses of undernourished mothers, but body weight was decreased at birth. Serum IGF-II decreased at 18 and 19 days of gestation in fetuses from undernourished mother, and increased at 18, 19 and 21 days in fetuses from diabetic mothers. Serum IGFBPs of low molecular weight (IGFBP-1 and IGFBP-2) increased in the three fetal populations studied, although no changes in serum IGFBPs were found from the effect of undernutrition or diabetes, but fetal liver IGFBP-1 mRNA expression was found to decreased in undernourished and diabetic animals as compared with controls. In neonatal rats, body weight, insulinemia and serum GH decreased in both undernourished and diabetic rats vs controls, while glycemia decreased in the undernourished and increased in the diabetic group. Serum IGF-II decreased only in diabetic rats and serum IGF-I decreased in both groups. The neonatal serum 30 kDa complex (IGFBP-1 and -2) also increased in undernutrition and diabetes parallel to the expression of mRNA. But, taken together, the changes in IGFBP peptide levels and liver mRNA expression strongly suggest that the 30 kDa complex seems to be composed mostly of IGFBP-1 in the diabetic group and of both IGFBP-1 and -2 in the undernourished animals. The studies of liver mRNA expression of IGFs and IGFBPs confirm the different metabolic control mechanism for the availability of IGFs by the IGFBPs, depending on the animal's maturity. The different adaptation shown by the diabetic neonatal population was confirmed by correlation studies between body weight, glycemia, insulinemia, IGF-I and IGFBPs. The different mechanism of adaptation in diabetic vs undernourished rats seems to be probably due to the decisive role played by hyperglycemia in the diabetic population, and also shows the crucial influence of nutritional status on IGFs and IGFBPs.

Interaction between malnutrition and ovarian hormones on the systemic IGF-I axis

“…Undernutrition, or poor nutrition, inhibits growth in the laboratory rat (5,10,11) and is one of the major causes of short stature in humans (31,32). In agreement, we now show that undernutrition of peripubertal rats significantly reduced body weight, which at this age is directly proportional to linear growth (33).…”

“…Western ligand blots were performed as previously described (5,23). Briefly, sera were diluted in sample buffer (Tris -HCl, 0.625 mol/l, pH 6.8; 10% (v/v) glycerol; 2% SDs and 0.0125% bromophenol blue) and 2.5 ml serum were submitted to SDS-PAGE under non-reducing conditions (to prevent denaturation of IGFBPs) on a 10% polyacrylamide gel.…”

“…Solution hybridization/RNase protection assays were performed as previously described (5,25). Autoradiography was performed at 2 70 8C against Hyperfilm MP between intensifying screens.…”

“…In addition, synergistic effects and cross-reactivity, with one factor activating or requiring the presence of receptors of the other, have been demonstrated in certain cell types (16,18). Sex steroids and IGF-I have also been reported to have numerous points of interaction in their intracellular signaling mechanisms in many tissues (5,22). Hence, the physiological response of one system may depend, at least in part, upon the condition or hormone levels of the other system.…”

Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto–Kakizaki rat model of type 2 diabetes

“…Determination of serum IGF2 and IGF1 Serum IGF2 was measured by radioreceptor assay as previously described [17,18]. Serum IGF1 was measured by enzyme immunoassay using a rat IGF1 enzyme immunoassay kit (Diagnostic Systems Laboratories, Webster, TX, USA).…”