Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations.
Janssen. Joseph A M J L JA; Hofland. Leo J LJ; Strasburger. Christian J CJ; van den Dungen. Elisabeth S R ES; Thevis. Mario M
Key Findings
- Full‑length MGF fully activates the IGF‑I receptor at high equimolar concentrations, matching IGF‑I’s maximal effect.
- Full‑length MGF’s EC50 for IGF‑I receptor activation is ~7.8 nmol/L, about nine times higher than IGF‑I’s 0.86 nmol/L, indicating lower potency.
- Full‑length MGF also stimulates insulin receptors, with a stronger maximal effect on IR‑B than insulin itself, while short MGF and Goldspink‑MGF showed no IGF‑I receptor activity.
Practical Outcomes
- If you’re considering MGF for IGF‑I‑like benefits, expect to need much higher doses than IGF‑I to see similar effects, and be aware it may also influence insulin signaling. The findings are limited to cell assays, so real‑world efficacy and safety remain uncertain; start low, monitor, and await more in‑vivo data.
Summary
The study shows that the full‑length version of MGF can turn on the IGF‑I receptor just as strongly as regular IGF‑I, but you need a lot more of it to do so. It also hits insulin receptors, especially the B type, even better than insulin itself. Shorter MGF forms didn’t work on the IGF‑I receptor. This means the full‑length peptide has some IGF‑I‑like activity, but you’d likely need high doses, and it’s unclear how this translates to real‑world use.
Abstract
To compare full-length mechano growth factor (full-length MGF) with human recombinant insulin-like growth factor-I (IGF-I) and human recombinant insulin (HI) in their ability to activate the human IGF-I receptor (IGF-IR), the human insulin receptor (IR-A) and the human insulin receptor-B (IR-B), respectively. In addition, we tested the stimulatory activity of human MGF and its stabilized analog Goldspink-MGF on the IGF-IR. The effects of full-length MGF, IGF-I, human mechano growth factor (MGF), Goldspink-MGF and HI were compared using kinase specific receptor activation (KIRA) bioassays specific for IGF-I, IR-A or IR-B, respectively. These assays quantify activity by measuring auto-phosphorylation of the receptor upon ligand binding. IGF-IR: At high equimolar concentrations maximal IGF-IR stimulating effects generated by full-length MGF were similar to that of IGF-I (89-fold vs. 77-fold, respectively). However, EC50 values of IGF-I and full-length MGF for the IGF-I receptor were 0.86 nmol/L (95% CI 0.69-1.07) and 7.83 nmol/L (95% CI: 4.87-12.58), respectively. No IGF-IR activation was observed by human MGF and Goldspink-MGF, respectively. IR-A/IR-B: At high equimolar concentrations similar maximal IR-A stimulating effects were observed for full -length MGF and HI, but maximal IR-B stimulation achieved by full -length MGF was stronger than that by HI (292-fold vs. 98-fold). EC50 values of HI and full-length MGF for the IR-A were 1.13 nmol/L (95% CI 0.69-1.84) and 73.11 nmol/L (42.87-124.69), respectively; for IR-B these values were 1.28 nmol/L (95% CI 0.64-2.57) and 35.10 nmol/L (95% 17.52-70.33), respectively. Full-length MGF directly stimulates the IGF-IR. Despite a higher EC50 concentration, at high equimolar concentrations full-length MGF showed a similar maximal potency to activate the IGF-IR as compared to IGF-I. Further research is needed to understand the actions of full-length MGF in vivo and to define the physiological relevance of our in vitro findings.
Study Information
pubmed
2016
2016-03-18T00:00:00.000Z
10.1371/journal.pone.0150453
5
27