Sleeve Gastrectomy-Induced Weight Loss Increases Insulin Clearance in Obese Mice

Sleeve gastrectomy (SG) successfully recovers metabolic homeostasis in obese humans and rodents while also resulting in the normalization of insulin sensitivity and insulinemia. Reduced insulin levels have been attributed to lower insulin secretion and increased insulin clearance in individuals submitted to SG. Insulin degradation mainly occurs in the liver in a process controlled, at least in part, by the insulin-degrading enzyme (IDE). However, research has yet to explore whether liver IDE expression or activity is altered after SG surgery. In this study, C57BL/6 mice were fed a chow (CTL) or high-fat diet (HFD) for 10 weeks. Afterward, the HFD mice were randomly assigned to two groups: sham-surgical (HFD-SHAM) and SG-surgical (HFD-SG). Here, we confirmed that SG improves glucose–insulin homeostasis in obese mice. Additionally, SG reduced insulinemia by reducing insulin secretion, assessed by the analysis of plasmatic C-peptide content, and increasing insulin clearance, which was evaluated through the calculation of the plasmatic C-peptide:insulin ratio. Although no changes in hepatic IDE activity were observed, IDE expression was higher in the liver of HFD-SG compared with HFD-SHAM mice. These results indicate that SG may be helpful to counteract obesity-induced hyperinsulinemia by increasing insulin clearance, likely through enhanced liver IDE expression.