Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
Skip to main content

We examined the effects of insulin-like growth factors (IGFs) and insulin on erythropoietin (EPO) production by human hepatoma cells (Hep G2). Compared with normoxia (20% O2), EPO production by Hep G2 cells during a 72-h incubation was stimulated fivefold by exposure to low oxygen tension (1% O2) and nearly threefold by exposure to cobalt chloride (100 μM). IGF-I caused a concentration-dependent attenuation of EPO formation under normoxic conditions and inhibited (maximally 50%) EPO production stimulated by either low oxygen tension or cobalt [half-maximal effect (ED50) ≃ 5 nM]. The increase of EPO mRNA levels in response to hypoxia was significantly reduced by IGF-I. Similarly to IGF-I, IGF-II (ED50≃ 8 nM) and insulin (ED50≃ 80 nM) also inhibited EPO formation in Hep G2 cells. IGF-I (100 pM-100 nM) stimulated the incorporation of radiolabeled alanine as a measure for total protein synthesis,3H-labeled thymidine incorporation into DNA, and glycogen synthesis at 20 and 1% O2in a concentration-dependent fashion. IGF-I exhibited a high affinity for the IGF-I receptor (apparent K(d) ≃ 3 nM). Unlabeled insulin was >100-fold less potent than IGF-I in competing for125I-IGF-I binding (apparent K(d) ≃360 nM). Conversely, insulin bound to the insulin receptor with high affinity (apparent K(d) ≃ 0.3 nM), whereas IGF-I was <1% as potent in competing for125I-insulin binding. In summary, IGFs and insulin exert a negative control function on oxygen-regulated EPO production in Hep G2 cells. The inhibitory effect of IGFs and insulin on EPO formation appears to be mediated via the IGF-I receptor.

Type

Journal article

Journal

American Journal of Physiology - Cell Physiology

Publication Date

01/01/1992

Volume

263