Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2

Abstract

Whether insulin, at physiological concentrations, has direct effects on vascular smooth muscle cells (VSMCs) remains controversial. Our aim was to characterize the mechanism for insulin resistance in VSMCs. For comparison, the effects of IGF1 and IGF2 were also studied. Cultured human aortic smooth muscle cells (HASMC) were used. Receptor mRNA was analyzed by quantitative reverse transcription PCR and receptor protein by ELISA and western blot. Biological effects were studied by thymidine incorporation and glucose accumulation. In HASMC, both mRNA and protein expression of IGF1 receptors (IGF1R) were fivefold higher compared to insulin receptor (IR). IR isoform A mRNA was 13-fold more expressed than IR isoform B. IR and IGF1R co-precipitated, indicating the presence of hybrid IR/IGF1R. Phosphorylation of the IGF1R b-subunit was obtained by IGF1 10 K9

Thiazolidinediones Up-regulate Insulin-like Growth Factor-1 Receptor via a Peroxisome Proliferator-activated Receptor γ-Independent Pathway

“…Consistent with a previous report (33), human aortic SMCs responded to physiological doses of IGF-1 but not to insulin (supplemental Fig. S1).…”

Role of UDP-N-Acetylglucosamine (GlcNAc) and O-GlcNAcylation of Hyaluronan Synthase 2 in the Control of Chondroitin Sulfate and Hyaluronan Synthesis

“…In fact, whether insulin, at physiological concentrations, has direct effects on vascular SMCs remains controversial (37,38). In light of these considerations, the high concentration of glucose in the cell cultures did not induce hyperglycemic conditions in cell cytoplasm and consequently did not increase intracellular UDP-GlcNAc concentration.…”

IGF-1 deficiency in a critical period early in life influences the vascular aging phenotype in mice by altering miRNA-mediated post-transcriptional gene regulation: implications for the developmental origins of health and disease hypothesis

“…Vascular endothelial and smooth muscle cells abundantly express IGF1R and are more sensitive to IGF-1 than to insulin (Chisalita and Arnqvist 2004;Chisalita et al 2009;Johansson et al 2008). Several lines of evidence suggest that normal developmental IGF-1 levels promote vascular health later in life ).…”

“…The cardiovascular system is an especially important target organ for IGF-1 (Chisalita and Arnqvist 2004;Chisalita et al 2009;Johansson et al 2008;Li et al 2007;Toth et al 2014Toth et al , 2015, and there is increasing evidence suggesting that early-life IGF-1 levels may determine cardiovascular health in later life (Sonntag et al 2005a. Accordingly, previous studies demonstrate that rodent models with developmental IGF-1 deficiency exhibit a cardiac and/or vascular phenotype in adulthood Helms et al 2010;Reddy et al 2014).…”