Humanin is a tiny protein made by mitochondria that helps protect cells and may boost how the body handles insulin. Studies in cells and animals suggest it can make tissues more insulin‑sensitive, keep pancreatic beta cells alive, and possibly slow down the development of type‑2 diabetes, which is linked to aging. However, most evidence is still pre‑clinical, and there’s no clear dosing guide for humans yet.

Humanin (HN) is a 24-amino acid mitochondrial-derived polypeptide with cyto-protective and anti-apoptotic effects that regulates the mitochondrial functions under stress conditions. Accumulating evidence suggests the role of HN against age-related diseases, such as Alzheimer's disease. The decline in insulin action is a metabolic feature of aging and thus, type 2 diabetes mellitus is considered an age-related disease, as well. It has been suggested that HN increases insulin sensitivity, improves the survival of pancreatic beta cells, and delays the onset of diabetes, actions that could be deployed in the treatment of diabetes. The aim of this review is to present the <i>in vitro</i> and <i>in vivo</i> studies that examined the role of HN in insulin resistance and diabetes and to discuss its newly emerging role as a therapeutic option against those conditions.