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

• Pregnancy-associated plasma protein-A2 (PAPP-A2) is a protease of IGFBP-5.
• Deletion of Pappa2 increased circulating IGFBP-5 and IGF-I and decreased IGFBP-3.
• Deletion of Pappa2 did not affect fasting glucose levels or glucose tolerance.
• Deletion of Pappa2 had no effect on adiposity on a high-fat diet.

ObjectiveInsulin-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.DesignPostnatal 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.ResultsCirculating 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 2 g 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.ConclusionsDespite 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.