GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
The intestinal uptake of "enzymatically-stable" peptide drugs in rats as influenced by D-glucose in situ.
Hu. Z Z; Tse. E G EG; Monkhouse. D C DC; Oh. C K CK; Fleisher. D D
Key Findings
- Luminal D‑glucose increases jejunal permeability for tiny di‑ and tri‑peptides via solvent drag.
- The same glucose effect does NOT improve absorption of larger peptides such as the hexapeptide GHRP‑6 or octreotide.
- Glucose causes net water absorption for all tested peptides, but water flux alone isn’t enough to move bigger peptides across the gut wall.
- A non‑metabolizable glucose analogue suggests that an enhanced proton gradient contributes to carrier‑mediated transport of the small peptides.
Practical Outcomes
- Taking GHRP‑6 with carbs or glucose won’t make it absorb better when taken orally. For biohackers wanting to use GHRP‑6, injectable or alternative delivery routes (sublingual, nasal, or peptide‑modifying formulations) remain necessary. The study reinforces that gut‑based tricks work only for very small peptides, not for most therapeutic peptides.
Summary
In rats, adding glucose to the gut helps the body absorb very small peptide drugs, but it doesn’t boost the uptake of larger ones like GHRP‑6. Even though glucose pulls water into the intestine, the size of GHRP‑6 still blocks it from getting through.
Abstract
In previous in situ and in vivo rat perfusion studies, the intestinal absorption of several low molecular weight drugs was increased by the presence of luminal D-glucose. The intent of this study was to determine the potential of this fed-state effect to improve the intestinal uptake of poorly permeable, small peptide and peptide-like drugs. Jejunal wall permeabilities (Pw*) of di-(D-kyotorphin), tri-(cephradine), hexa-(growth hormone releasing peptide, GHRP-6) and octa-(octreotide, a somatostatin analogue) peptides and corresponding net water fluxes were determined in rats using an in situ single-pass perfusion technique. Glucose was shown to enhance the uptake of the smaller (di- and tri-) peptides but not the larger peptides despite the fact that glucose elicited a significant net water absorption with each of the four peptide drugs. It is concluded that glucose enhances jejunal permeabilities of smaller peptides by solvent drag and the enhancement is limited in situ by peptide molecular size. The studies with nonmetabolizable 3-O-methylglucose suggest that the augmentation of the proton gradient across the transmucosal membrane by glucose contributes to the carrier-mediated transport observed with the smaller peptides.
Study Information
pubmed
1994
10.1016/0024-3205(94)90132-5
4
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