Journal of Endocrinology. 2002;174(2).
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.