Key result
Human micro- and macrovascular endothelial cells express more IGF-IR than IR, and while glargine has higher affinity than insulin for IGF-IR, it likely has no effect on DNA synthesis in vivo.
Human micro- and macrovascular endothelial cells express more IGF-IR than IR, and while glargine has higher affinity than insulin for IGF-IR, it likely has no effect on DNA synthesis at in vivo concentrations.
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Reassures on glargine endothelial safety at physiologic concentrations; leaves open human in vivo confirmation.
Micro- and macroangiopathy are major causes of morbidity and mortality in patients with diabetes. Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. Cultured human dermal microvascular endothelial cells (HMVEC) and human aortic endothelial cells (HAEC) were used. Gene expression was measured by quantitative real-time RT-PCR and receptor protein by ligand-binding assay. Phosphorylation of IGF-IR beta-subunit was analyzed by immunoprecipitation and Western blot. Glucose metabolism and DNA synthesis was assessed using [(3)H]glucose and [(3)H]thymidine incorporation, respectively. We detected gene expression of IGF-IR and IR in HAEC and HMVEC. IGF-IR gene expression was severalfold higher than that of IR. The specific binding of (125)I-IGF-I was higher than that of (125)I-insulin in HAEC and HMVEC. Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. Human micro- and macrovascular endothelial cells express more IGF-IR than IR. IGF-I and high concentrations of glargine and insulin activates the IGF-IR. Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo.
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Chisalita et al. (2004) studied Diabetes (in vitro endothelial cell study). IGF-I, insulin, and glargine was evaluated on Gene expression, receptor protein binding, phosphorylation, and DNA synthesis/glucose metabolism. Human micro- and macrovascular endothelial cells express more IGF-IR than IR, and while glargine has higher affinity than insulin for IGF-IR, it likely has no effect on DNA synthesis in vivo.
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