GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin protects human umbilical vein endothelial cells against high glucose-induced apoptosis via mTOR/P70S6K signaling pathway.
Zhu. Jianhua J; Zheng. Chenghong C; Chen. Jie J; Luo. Jing J; Su. Bintao B; Huang. Yan Y; Su. Wen W; Li. Zixi Z; Cui. Tianpen T
Key Findings
- Ghrelin reduces high‑glucose‑induced apoptosis in human umbilical vein endothelial cells.
- The protective effect requires activation of the GHS‑R1a receptor and the mTOR/P70S6K signaling cascade.
- Ghrelin increases the anti‑apoptotic Bcl‑2/Bax protein ratio, and blocking mTOR or the receptor eliminates the benefit.
Practical Outcomes
- For biohackers, this suggests ghrelin might help protect blood‑vessel health under high‑sugar conditions, but the evidence is limited to cell‑culture experiments. No human dosing, safety, or administration guidelines are provided, so it’s not ready for direct use. It does, however, highlight the mTOR pathway as a potential target for metabolic‑health interventions.
Summary
The study shows that the hormone ghrelin can protect blood vessel cells from dying when they’re exposed to high sugar levels. It does this by turning on a cell‑growth pathway (mTOR/P70S6K) and increasing the balance of protective proteins (Bcl‑2 vs. Bax). Blocking ghrelin’s receptor or the mTOR pathway stops this protection, proving the effect is real in the lab.
Abstract
Ghrelin exhibits its biological effect through binding to the growth hormone secretagogue 1a receptor (GHS-R1a). Recently, it has been reported that ghrelin has an anti-apoptotic effect in several cell types. However, the molecule mechanisms underlying the anti-apoptotic effect of ghrelin remain poorly understood. In this study, we investigated the intracellular mechanisms responsible for anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with ghrelin inhibited high glucose-induced cell apoptosis. Ghrelin stimulated the rapid phosphorylation of mammalian target of rapamycin (mTOR), P70S6K and S6. The GHS-R1a-specific antagonist [D-Lys3]-GHRP-6 abolished the anti-apoptotic effect and inhibited the activation of mTOR, P70S6K, S6 induced by ghrelin. Pretreatment of cells with specific inhibitor of mTOR blocked the anti-apoptotic effect of ghrelin. In addition, ghrelin protected HUVECs against high glucose induced apoptosis by increasing Bcl-2/Bax ratio. Taken together, our results demonstrate that ghrelin produces a protective effect on HUVECs through activating GHS-R1a and mTOR/P70S6K signaling pathway mediates the effect of ghrelin. These observations suggest that ghrelin may act as a survival factor in preventing HUVECs apoptosis caused by high glucose.
Study Information
pubmed
2013
2013-11-25T00:00:00.000Z
10.1016/j.peptides.2013.11.015
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