Pappa2 deletion alters IGFBPs but has little effect on glucose disposal or adiposity.

OBJECTIVE Insulin-like growth factor binding proteins (IGFBPs) are involved in glucose and lipid metabolism, and their actions are modulated by proteases. The aim of this study was to examine the effects of an IGFBP-5 protease, pregnancy associated plasma protein-A2 (PAPP-A2), on glucose metabolism and susceptibility to diet-induced obesity. DESIGN Postnatal growth, circulating IGF-I, IGFBP-3 and IGFBP-5 levels, and glucose tolerance were measured in Pappa2 deletion mice and littermate controls on a chow diet. Males were subsequently fed a high-fat diet for 8 weeks to measure weight gain and adiposity, as well as glucose tolerance in response to a metabolic challenge. RESULTS Circulating IGFBP-5 levels were ~2-fold higher in mice with no functional PAPP-A2 than in littermate controls, as expected. In contrast, circulating IGFBP-3 levels were reduced by ~15-fold, and total IGF-I levels were ~60% higher in Pappa2 deletion mice. There was no effect of Pappa2 deletion on fasting blood glucose levels or glucose clearance after intraperitoneal injection of 2g glucose/kg body weight in mice on a chow diet. In males on a high-fat diet, there was no difference between genotypes in weight gain or adiposity, adjusting for differences in initial body weight, or in fasting blood glucose or insulin levels, or in glucose clearance. CONCLUSIONS Despite a dramatic disruption of the balance between circulating IGF-I, IGFBP-3 and -5, we found no effects of Pappa2 deletion on glucose metabolism, weight gain or adiposity on a high-fat diet.