Ron Rosenfeld | PubMed Health

PubMed2004

IGFBPs and cancer.

The proposed insulin-like growth factor binding protein (IGFBP) superfamily are a group of secreted proteins that are structurally, functionally and evolutionarily related, and include six IGFBPs and over 10 IGFBP-related proteins. The IGFBPs have high affinities for insulin-like growth factors (IGFs), thereby modulating the mitogenic, anti-apoptotic and metabolic actions of IGFs. In addition, IGFBPs, particularly IGFBP-3, also have IGF-independent, anti-proliferative and pro-apoptotic functions. The IGFBPs are, in turn, modulated by proteolysis. Epidemiological data correlating serum IGF/IGFBP levels with the risk of several human cancers suggest a possible protective role for IGFBP-3. In vitro studies suggest that the potential protective effects of IGFBP-3 involve both IGF-dependent and IGF-independent mechanisms. Further studies are necessary to demonstrate whether the ability of IGFBPs to inhibit the proliferation of cancer cells under in vitro conditions has significant clinical implications.

Animals↗

PubMed2002

The effects of short-term administration of two low doses versus the standard GH replacement dose on insulin sensitivity and fasting glucose levels in young healthy adults.

GH has both diabetogenic and insulin-like actions. Supraphysiological GH doses are known to reduce insulin sensitivity (S(I)), but lower doses are less well studied. We therefore compared the effects of two physiological GH doses (intermediate, 0.0033 mg/kg x d; low, 0.0017 mg/kg x d) with the standard adult GH deficiency replacement dose (standard, 0.008 mg/kg x d) on S(I), beta-cell function, IGF-I, and IGF binding proteins (IGFBPs)-1 and -3 in healthy adults. Eleven healthy nonobese volunteers (4 males and 7 females, aged 21-38 yr) received 7 daily injections of the standard and intermediate GH doses, and 10 (5 males and 5 females, aged 21-38 yr) received the low dose. Fasting blood samples were collected daily (days 1-8). S(I) and beta-cell function were calculated using the Homeostasis model assessment. All GH doses increased IGF-I and IGFBP-3 levels, with the standard dose inducing the greatest rise (P < 0.001). At day 2 vs. baseline, all three doses increased the IGF-I/IGFBP-3 ratio, but only the standard dose lowered IGFBP-1 levels (P = 0.03). The standard dose reduced S(I) (P = 0.01), whereas the intermediate dose increased S(I) (P < 0.005) and lowered fasting insulin levels (P < 0.01). The low dose did not modify S(I), but reduced fasting glucose levels (P < 0.0001) and increased beta-cell function (P = 0.001). Males demonstrated higher IGF-I and IGFBP-3 responsiveness to the standard dose than females. Males also showed greater increase in S(I) and decrease in fasting glucose levels on both intermediate and low doses. In conclusion, the metabolic effects of GH are dose- and gender-dependent. The standard adult GH deficiency replacement dose induced insulin resistance, whereas lower doses improved S(I), especially in males. The low GH dose lowered fasting glucose levels and could represent the optimal dose to stimulate beta-cell function without compromising S(I) in insulin-resistant GH-deficient adults.

Adult↗