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insulin-like growth factor-1; mechano growth factor; MGF; somatomedin-C (IGF1, IBP1)

Function: - structurally & functionally related to insulin but with a much higher growth-promoting activity - 85% bound in molecular complex with IGF-binding protein 3 & acid labile subunit glycoprotein. - may enhance growth of tumors. [3] - may be a physiological regulator of glucose transport & glycogen synthesis in osteoblasts Structure: belongs to the insulin family Compartment: - plasma - secreted by liver in response to growth hormone Alternate splicing: - forms IGF-1A & IGF-1B - named isoforms=4 Expression: - secreted by liver in response to growth hormone Pathology: - IGF1 deficiency is an autosomal recessive disorder - low serum IGF-1 levels correlate with increased sarcopenia prevalence & reduced muscle mass in elderly populations. - low plama IGF-1 levels predicts life expectancy in exceptionally long-lived women & persons of either gender with history of cancer [8] Pharmacology: - recombinant human IGF-1 (mecasermin) - FDA-approved for treating growth failure in pediatric patients with severe primary IGF-1 deficiency or growth hormone gene deletion who have developed neutralizing antibodies to growth hormone - off label uses - severe insulin resistance syndromes - - type A insulin resistance, Rabson-Mendenhall syndrome, Donohue's syndrome - bypasses insulin receptor defects [13] - growth hormone insensitivity syndrome, including Laron syndrome [12]

Related

IGF-1 gene insulin-like growth factor (IGF)-1 or somatomedin C in serum insulin-like growth factor [IGF]-1 receptor (somatomedin-C receptor, CD221, IGF1R) somatotropin; growth hormone; somatropin (GH)

Specific

mecasermin (Increlex, Insmed, recombinant IGF1)

General

multisubunit protein peptide precursor somatomedin

Properties

SIZE: entity length = 195 aa MW = 22 kD MW = 7 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-21} B {49-77} MOTIF: cysteine residue {C54} MODIFICATION: cysteine residue {C96} cysteine residue {C66} MODIFICATION: cysteine residue {C109} C {78-89} A {90-110} MOTIF: cysteine residue {C95} MODIFICATION: cysteine residue {C100} cysteine residue {C96} MODIFICATION: cysteine residue {C54} cysteine residue {C100} MODIFICATION: cysteine residue {C95} cysteine residue {C109} MODIFICATION: cysteine residue {C66} D {111-118} SECRETED-BY: macrophage GENE: IGF-1 gene

Database Correlations

OMIM correlations UniProt P05019 Pfam PF00049 Entrez Gene 3479 Kegg hsa:3479

References

  1. Henderson B & Blake S Therapeutic potential of cytokine manipulation TIPS 13:145 1992 PMID: 1589908
  2. Solomon DH, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  3. LeRoith D IGF-1, Cancer and Aging Aging: Mechanisms and Prevention 34th Annual Meeting of the American Aging Association June 3-6, 2005, Oakland CA
  4. UniProt :accession P05019
  5. SHMPD; Note: Singapore human mutation andpolymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=HLA-DQB1
  6. NIEHS-SNPs http://egp.gs.washington.edu/data/igf1/
  7. Wikipedia; Note: insulin-like growth factor 1 entry http://en.wikipedia.org/wiki/insulin-like_growth_factor_1
  8. Milman S, Atzmon G, Huffman DM et al Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. 2014 Aug;13(4):769-71. PMID: 24618355 Free PMC Articl
  9. Ferrari U, Schmidmaier R, Jung T et al IGF-I/IGFBP3/ALS Deficiency in Sarcopenia: Low GHBP Suggests GH Resistance in a Subgroup of Geriatric Patients. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1698-e1707. PMID: 33378445
  10. Jiang JJ, Chen SM, Chen J, Wu L, Ye JT, Zhang Q. Serum IGF-1 levels are associated with sarcopenia in elderly men but not in elderly women. Aging Clin Exp Res. 2022 Oct;34(10):2465-2471. PMID: 35962897
  11. Bian A, Ma Y, Zhou X, Guo Y, Wang W, Zhang Y, Wang X. Association between sarcopenia and levels of growth hormone and insulin-like growth factor-1 in the elderly. BMC Musculoskelet Disord. 2020 Apr 7;21(1):214. PMID: 32264885 PMCID: PMC7140321 Free PMC article. https://pmc.ncbi.nlm.nih.gov/articles/PMC7140321/
  12. Ranke MB. Insulin-like growth factor-I treatment of growth disorders, diabetes mellitus and insulin resistance. Trends Endocrinol Metab. 2005 May-Jun;16(4):190-7. PMID: 15860416 Review.
  13. McDonald A, Williams RM, Regan FM, Semple RK, Dunger DB. IGF-I treatment of insulin resistance. Eur J Endocrinol. 2007 Aug;157 Suppl 1:S51-6. PMID: 17785698 Review.

Component-of

IGF-1/IGF binding protein 3/acid-labile subunit glycoprotein