Pharmacokinetics and tissue distribution of humanin and its analogues in male rodents.
Chin. Yung-Ping YP; Keni. Jyotsna J; Wan. Junxiang J; Mehta. Hemal H; Anene. Francine F; Jia. Yue Y; Lue. Yan-He YH; Swerdloff. Ronald R; Cobb. Laura J LJ; Wang. Christina C; Cohen. Pinchas P
Key Findings
- Humanin analogues HNG and HNGF6A have a longer half‑life in mouse blood than native humanin
- Injecting HNG reduces circulating IGF‑1 and IGFBP‑3 levels over time
- In rats, humanin is highest in plasma, detectable in liver, but not in brain or heart, showing species‑specific distribution
Practical Outcomes
- For biohackers, the take‑away is that engineered humanin peptides may stay active longer in the body, which could make them more effective than the natural form. However, the study used mouse/rat injections, so there’s no direct human dosing guidance yet. It suggests potential for diabetes‑related benefits, but more human research is needed before trying it on yourself.
Summary
This study looked at how long humanin and its tweaked versions stay in the blood of mice and rats after an injection. The modified versions (HNG and HNGF6A) lasted longer than the natural peptide, and giving HNG lowered some growth‑factor proteins (IGF‑1 and IGFBP‑3). In rats, humanin was mostly found in the blood and liver, not in the brain or heart. The work hints that these engineered peptides could be more useful as drugs, especially for diabetes, but it doesn’t give clear dosing advice for people.
Abstract
Humanin (HN) is a novel 24-amino acid mitochondrial-derived peptide that has demonstrated diverse cytoprotective effects, including an emerging role in diabetes. The purpose of this study was to examine the pharmacokinetics of humanin analogues, which show great potential as therapeutic agents (HNG and the non-IGFBP-3 binding, HNGF6A). 11-week-old male IGFBP-3(-/-) and wild type (WT) mice were divided into 3 groups: WT mice treated with HNG, WT mice treated with HNGF6A, and IGFBP-3(-/-) mice treated with HNG. Plasma was obtained from mice following ip injection with HN analogues, and HN levels were measured with ELISA. WT mice treated with HNGF6A and IGFBP-3(-/-) mice treated with HNG displayed a longer half-life of HN compared with WT mice treated with HNG. Following HNG injection, both IGF-1 and IGFBP-3 levels decreased over time. Adult male Sprague Dawley rats were also ip injected with HNG, and HN levels were measured in various tissues (plasma, liver, heart, and brain) by ELISA. The half-life of HN was found to be longer in rats compared with mice. In rats, HN levels were found to be highest in plasma, present in liver, and undetectable in brain or heart. The current study provides evidence of HN and IGFBP-3 association in the circulation and suggests that native HN may modulate the distribution of IGF-1 and IGFBP-3. The results also demonstrate varying kinetic profiles of HN analogues and interspecies variation in rodents. Sustainable levels of circulating HN measured in plasma underline the potential value of HN analogues as a new therapeutic intervention in the treatment of diabetes.
Study Information
pubmed
2013
2013-07-08T00:00:00.000Z
10.1210/en.2012-2004
53
26