GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type 1a and the corticotropin releasing factor 2 receptor.
Gauna. Carlotta C; Delhanty. Patric J D PJ; van Aken. Maarten O MO; Janssen. Joop A M J L JA; Themmen. Axel P N AP; Hofland. Leo J LJ; Culler. Michael M; Broglio. Fabio F; Ghigo. Ezio E; van der Lely. Aart Jan AJ
Key Findings
- Both unacylated ghrelin (UAG) and acylated ghrelin (AG) stimulate insulin secretion in INS‑1E rat insulinoma cells at nanomolar concentrations.
- AG‑induced insulin release is blocked by GHS‑R1a antagonists ([d‑Lys(3)]GHRP‑6 and BIM28163), confirming it acts through the classic ghrelin receptor.
- UAG‑induced insulin release is not affected by GHS‑R1a or CRF2R antagonists, indicating it uses a separate, unidentified receptor.
Practical Outcomes
- For biohackers, the data suggest that unacylated ghrelin could potentially improve insulin release without engaging the usual ghrelin receptor, but the evidence is limited to rat cells and an unknown mechanism. Until human studies confirm safety and efficacy, it isn’t ready for direct supplementation or dosing protocols. The findings do, however, reinforce that GHRP‑6‑type antagonists can block acylated ghrelin effects, which may be relevant for fine‑tuning ghrelin‑based interventions.
Summary
The study shows that both the regular (acylated) and the non‑acylated forms of ghrelin can make rat insulin‑producing cells release more insulin. The regular form works through the known ghrelin receptor (GHS‑R1a) and can be blocked by GHRP‑6‑type antagonists, while the non‑acylated form acts via a different, still‑unknown receptor.
Abstract
Both unacylated ghrelin (UAG) and acylated ghrelin (AG) exert metabolic effects. To investigate the interactions between AG and UAG on ghrelin receptors we evaluated the effects of AG and UAG on INS-1E rat insulinoma cells, using insulin secretion after 30min static incubation as a read-out. A possible involvement of the growth hormone secretagogue receptor type 1a (GHS-R1a) or the corticotropin-releasing factor 2 (CRF2) receptor (CRF2R), as a putative receptor for UAG, was also studied determining their mRNA expression and the functional effects of receptor antagonists on insulin release. Both UAG and AG stimulated insulin release dose-dependently in the nanomolar range. The AG-induced insulin output was antagonized by two GHS-R1a antagonists ([d-Lys(3)]GHRP-6 and BIM28163), which did not block UAG actions. These effects occurred in the presence of low levels of GHS-R1a mRNA. Neither CRF2R expression nor effects of the CRF2R antagonist (astressin(2)B) on insulin output were observed. In conclusion, we provide a sensitive and reproducible assay for specific effects of UAG, which in this study is responsible for insulin release by INS-1E cells. Our data support the existence of a specific receptor for UAG, other than the CRF2R and GHS-R1a. The stimulatory effect on insulin secretion by AG in this cell line is mediated by the GHS-R1a.
Study Information
pubmed
2006
2006-04-27T00:00:00.000Z
10.1016/j.mce.2006.03.040
85
41