Metabolic improvement after gastric bypass correlates with changes in IGF-regulatory proteins stanniocalcin-2 and IGFBP-4

Pregnancy-associated plasma protein-A (PAPP-A) is an enzyme that increases IGF-activity through cleavage of IGF-binding proteins (IGFBPs), primarily IGFBP-4, whereby bound IGF-I becomes released as a free molecule. The enzymatic activity of PAPP-A is irreversibly suppressed by the glycoprotein stanniocalcin-2 (STC2). Pre-clinical and clinical studies suggest that the STC2 – PAPP-A – IGFBP-4 axis is important in controlling local IGF-action. STC2, PAPP-A and IGFBP-4 are expressed in adipose tissue, and as bariatric surgery markedly reduces the amount of fat, we found it relevant to study the impact of Roux-en-Y gastric bypass (RYGB) on circulating concentrations of this IGF-regulatory network. Analysis of fasting blood samples from 20 obese subjects, hereof 10 with preoperative type 2 diabetes, investigated before RYGB, and 1 week, 3 months and 12 months post-surgery. Members of the IGF-system were analyzed by immunoassays, bioactive IGF by cell-based IGF-I receptor activation assay. We compared changes in IGF-system components with changes in fasting plasma insulin and glucose, and HbA1c. PAPP-A remained unchanged, but STC2 decreased following RYGB (p