In a rat study, a modified version of the mitochondrial peptide humanin (called S14G‑humanin) was given daily for 16 weeks and it helped reverse many signs of diabetic kidney damage, including high blood sugar, kidney waste markers, and inflammation. However, the work was done in animals, using injections that aren’t practical for people, and the exact dose for humans is unknown, so it’s more of a promising clue than a ready‑to‑use protocol.

Diabetes mellitus (DM) is associated with numerous complications, including nephropathy, which principally occur due to hyperglycemia-induced oxidative stress and inflammation. Humanin (HN), a novel peptide generated from mitochondria, has anti-oxidant and anti-inflammatory potential as observed in different disease models. However, role of HN in diabetic nephropathy (DN) has not yet been explored. This study aimed to evaluate biochemical and molecular aspects of the effects of HN analog, Humanin-glycine ([S14G]-humanin) on streptozotocin (STZ)-induced rat model of DN. Ninety Sprague Dawley (SD) rats were randomly segregated into three groups - A (control), B (disease control) and C (treatment). DM type-I was induced in group B and C via single intra-peritoneal dose of STZ (45 mg/Kg). Seven days following STZ injection, rats were deemed diabetic if their blood glucose level was > 250 mg/dL. Subsequently, diabetic rats in group C were injected with [S14G]-humanin intra-peritoneally (0.4 mg/Kg/day) for sixteen weeks. Biochemical analysis revealed that diabetic rats had markedly elevated levels of serum glucose, creatinine, BUN, TNF-α, and kidney tissue SOD. Whereas, significant decline was detected in serum insulin and albumin levels. All these parameters were significantly reversed in group C after administering [S14G]-humanin. Moreover, qRT-PCR analysis displayed up-regulation of pro-inflammatory (IL-18, IL-6, IL-1α, IL-1β, TNF-α) and down-regulation of anti-inflammatory cytokines (IL-10, IL-1RN, IL-4) in diabetic rats (group B). [S14G]-humanin treatment significantly reversed the expression of IL-18 and IL-1α, however, change in relative expression of IL-6, IL-1β, TNF-α and anti-inflammatory cytokines was insignificant (group C). Conclusively, the findings of this study depicted potential therapeutic role of [S14G]-humanin in pre-clinical rodent model of DN.