The insulin inhibitory receptor (inceptor) was recently identified as a key terminator of insulin and insulin-like growth factor 1 receptor (INSR/IGF1R) signaling in pancreatic 𝛽-cells12. Yet, the relevance of 𝛽-cell inceptor for glucose regulation through the INS1R/IGF1R axis has only been demonstrated for normoglycemic and insulin sensitive lean mice, questioning whether inceptor regulation of INS1R/IGF1R action also plays a role in glucose metabolism under conditions of diet-induced obesity and insulin resistance. Here we demonstrate that whole-body germline loss of inceptor improves glucose metabolism in diet-induced obese mice with only minimal effects on weight and body composition. To assess the effect in different tissues we performed proteomics in the global, neuronal and beta cell specific mouse knock-outs.