GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Exogenous and endogenous ghrelin counteracts GLP-1 action to stimulate cAMP signaling and insulin secretion in islet β-cells.
Damdindorj. Boldbaatar B; Dezaki. Katsuya K; Kurashina. Tomoyuki T; Sone. Hideyuki H; Rita. Rauza R; Kakei. Masafumi M; Yada. Toshihiko T
Key Findings
- Endogenous and added ghrelin reduce GLP‑1‑stimulated insulin secretion and cAMP production in pancreatic beta‑cells.
- Ghrelin also dampens calcium signals that are important for insulin release.
- Blocking the ghrelin receptor with D‑lys(3)‑GHRP‑6 markedly enhances GLP‑1’s insulinotropic effects in isolated rat islets.
Practical Outcomes
- If you’re using ghrelin‑mimicking peptides like GHRP‑6 for growth‑hormone or anti‑aging purposes, be aware they may blunt GLP‑1‑based glucose control and insulin release. Combining a ghrelin‑receptor antagonist (or avoiding high ghrelin activity) could improve the effectiveness of GLP‑1 drugs or natural GLP‑1 spikes from meals. This insight is mostly pre‑clinical, so apply caution and monitor blood‑sugar if experimenting.
Summary
The study shows that ghrelin (both naturally made in the pancreas and added from outside) can block the blood‑sugar‑lowering actions of GLP‑1, a hormone that boosts insulin release. When a ghrelin‑receptor blocker (D‑lys(3)‑GHRP‑6) was used, GLP‑1’s ability to raise cAMP and trigger insulin was much stronger in rat islet cells.
Abstract
We studied interactive effects of insulinotropic GLP-1 and insulinostatic ghrelin on rat pancreatic islets. GLP-1 potentiated glucose-induced insulin release and cAMP production in isolated islets and [Ca(2+)](i) increases in single β-cells, and these potentiations were attenuated by ghrelin. Ghrelin suppressed [Ca(2+)](i) responses to an adenylate cyclase activator forskolin. Moreover, GLP-1-induced insulin release and cAMP production were markedly enhanced by [D-lys(3)]-GHRP-6, a ghrelin receptor antagonist, in isolated islets. These results indicate that both exogenous and endogenous islet-derived ghrelin counteracts glucose-dependent GLP-1 action to increase cAMP production, [Ca(2+)](i) and insulin release in islet β-cells, positioning ghrelin as a modulator of insulinotropic GLP-1.
Study Information
pubmed
2012
2012-06-29T00:00:00.000Z
10.1016/j.febslet.2012.06.034
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