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Insulin‐enhanced proliferation and viability of human umbilical vein endothelial cells
Author(s) -
Reilly Frank,
Shrader Carl,
Bailey Kelly,
Konat Gregory,
Cilento Eugene
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.925.1
Subject(s) - umbilical vein , insulin , insulin receptor , microbiology and biotechnology , growth factor , viability assay , biology , wound healing , human umbilical vein endothelial cell , insulin like growth factor , medicine , endocrinology , insulin resistance , receptor , in vitro , immunology , biochemistry
This investigation is a follow‐up to our previous in vivo studies revealing that rapid stretch increases gene‐specific tissue insulin in murine skin flaps, coincident with up‐regulation of key angiogenic effectors and enhanced vascular growth and wound healing. In the current study, we used human umbilical vein endothelial cells (HUVECs) as an in vitro model system to determine the role of insulin in endothelial cell proliferation and survival. MTT‐based colorimetric analyses demonstrated that insulin enhances proliferation and viability of HUVECs. Western blots revealed that insulin induces the up‐regulation and activation of mitogenic signaling intermediates in endothelial cells. Activated insulin and insulin growth factor receptors (pIR / pIGFR), protein kinase B (pAkt 308 , pAkt 473 ) and vascular endothelial growth factor (VEGF) were among the insulin‐responsive intermediates. Responses to insulin were abrogated by the inhibition of pIR / pIGFR or phosphoinositide‐3 kinase (PI3‐K), indicating that insulin‐induced proliferation and survival are mediated through IR / IGFR and PI3‐K effectors. These data provide new knowledge about the beneficial effects of insulin on vascular growth and tissue viability, providing a mechanistic link to improved blood flow and wound healing in acutely stretched skin. (Supported in part by the School of Engineering and Mineral Resources.)