IGF-binding protein-1 inhibits IGF effects on adipocyte function: implications for insulin-like actions at the adipocyte.
IGF action in vivo is acutely regulated by IGF-binding protein-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 (EC(50): 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 (EC(50): 10 nM) and inhibiting isoproterenol-induced lipolysis (EC(50): 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.
Siddals
K W
KW
Diabetes and Endocrinology, Hope Hospital, Salford M6 8HD, UK.
Westwood
M
M
Gibson
J M
JM
White
A
A
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D013002:Somatomedins / Q000378:metabolism*
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D008049:Lipase; D005947:Glucose