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IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte

Siddals, K W; Westwood, M; Gibson, J M; White, A

Journal of Endocrinology. 2002;174(2).

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Abstract

IGF action in vivo is acutely regulated by IGF-binding protem-1 (IGFBP-1) and its phosphorylation state is implicated in modulating these effects. Since IGFs have an important regulatory role in adipocyte function, we investigated the effects of phosphorylated IGFBP-1 (pIGFBP-1) and non-phosphorylated IGFBP-1 (npIGF BP-1) on 3T3-L1 preadipocyte proliferation and adipocyte metabolism. IGFs stimulated clonal expansion of 3T3-L1 cells (IGF-I more potently than IGF-II (EC50: 30 nM and 50 nM)). npIGFBP-1 inhibited IGF-I (50 nM) clonal expansion at a 5:1 molar ratio (P<0.01), whereas pIGFBP-1 (purified from HepG2 cell medium) abolished clonal expansion at a 1:1 molar ratio (P<0.005). In contrast, IGF-II-induced clonal expansion was inhibited 100% at a 1:1 molar ratio of npIGFBP-1. In mature adipocytes, IGF-I was equipotent with insulin in stimulating glucose uptake (EC50: 10 nM) and inhibiting isoproterenol-induced lipolysis (EC50: 15 nM). npIGFBP-1 completely reversed IGF-I effects at a 1:1 molar ratio (P<0.01). In summary, IGFs rather than insulin are potent regulators of clonal expansion in 3T3-L1 preadipocytes. Importantly, IGFs are equipotent with insulin in regulating adipocyte metabolism. IGFBP-1 inhibits IGF effects on preadipocyte proliferation and adipocyte metabolism, with pIGFBP-1 being more potent than npIGFBP-1 at inhibiting mitogenic actions. Since IGFBP-1 is acutely regulated by insulin, this could have important consequences in hyperinsulinaemic and insulin-resistant states.

Bibliographic metadata

Type of resource:
Content type:
Published date:
Volume:
174
Issue:
2
Digital Object Identifier:
10.1677/joe.0.1740289
ISI Accession Number:
ISI:000177623700015
Related website(s):
  • Related website <Go to ISI>://000177623700015
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:151214
Created by:
Gibson, Martin
Created:
15th January, 2012, 15:04:02
Last modified by:
Gibson, Martin
Last modified:
1st February, 2013, 19:48:49