Comparison of the insulinotropic activity of glucagon-superfamily peptides in rat pancreas perfusion.
Suzuki. S S; Kawai. K K; Ohashi. S S; Watanabe. Y Y; Yamashita. K K
Key Findings
- tGLP‑1 and GIP are the most potent insulin‑releasing peptides in the test, active at 0.1 nM.
- GRF‑1‑29 (and its shorter version GRF‑1‑27) required micromolar levels and still failed to stimulate insulin release.
- Specific amino‑acid positions (4 gly, 9 asp, 11 ser) are critical for insulinotropic activity across the peptide family.
Practical Outcomes
- For biohackers seeking to improve glucose control or beta‑cell function, GRF‑1‑29 is not a useful supplement. Focus on proven insulin‑secretagogues like GLP‑1 analogues or GIP‑based strategies instead. The study also highlights that small sequence tweaks can dramatically change a peptide’s metabolic impact.
Summary
In a rat pancreas test, the peptide GRF‑1‑29 (a growth‑hormone‑releasing factor) barely boosted insulin release, while well‑known hormones like GLP‑1, GIP and glucagon did so at much lower concentrations. This shows that GRF‑1‑29 is not an effective insulin‑stimulating agent.
Abstract
Previous studies have demonstrated that glucagon-superfamily peptides stimulate insulin release from the pancreatic islets in a glucose dependent manner. In this study we have carried out a structure-activity study of their insulinotropic activity using a rat pancreas perfusion with 5.5 mM glucose concentration. The following peptides were examined: glucagon-like peptide-1(7-36)amide (tGLP-1), glucagon, gastric inhibitory peptide (GIP), peptide having an amino-terminal histidine and carboxy-terminal isoleucine amide (PHI), vasoactive intestinal polypeptide (VIP), growth hormone releasing factor(1-29)amide (GRF), GRF(1-27)amide and synthetic hybrid-peptides of PHI-GRF, PHI(1-11)-GRF(12-27) and PHI(1-20)-GRF(21-27). Their potencies were evaluated as: tGLP-1 = GIP > glucagon > PHI = VIP > PHI(1-20)-GRF(21-27) > PHI(1-11)-GRF(12-27) >> GRF(1-29) = GRF(1-27). It is clear that 0.1 nM tGLP-1 stimulated insulin release, whereas 1 microM GRF(1-29) did not. These results indicate that 1) in addition to N-terminal amino acid (histidine or tyrosine), position 4 (glycine), position 9 (aspartic acid) and position 11 (serine) in the amino acid sequence are important for their insulinotropic activity, 2) not only the N-terminal portion but also the C-terminal portion of these peptides contribute to their insulinotropic activity.
Study Information
pubmed
1992
1992-10-01T00:00:00.000Z
10.1055/s-2007-1003362
14