INS and chronic kidney disease: Considering that the uremic milieu in CKD patients (CKD stage 4) has been associated with up-regulation of NRF2 [40], it is of interest that a recent investigation evaluating the humanin peptide and the mitochondrial open reading frame of 12S rRNA-c (MOTS-c) related to cell survival, suppression of apoptosis in oxidative stress or starvation, as well as enhanced insulin secretion and action found that patients with stage 5 CKD had increased circulating levels but reduced local muscle expression of humanin [41].