title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Joseph A M J L
authors.initials: JA
authors.lastname: Janssen
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.affiliation: Department of Medicine for Endocrinology, Diabetes and Nutritional Medicine Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Elisabeth S R
authors.initials: ES
authors.lastname: van den Dungen
authors.affiliation: Center for Preventive Doping Research - Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
mesh_terms: D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D007328:Insulin; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1