Abstract
Exogenous insulin use in patients with type 2 diabetes (DM2) has been associated with an increased risk of cardiovascular events. Through which mechanisms insulin may increase atherosclerotic plaque vulnerability is currently unclear. Because insulin has been suggested to promote angiogenesis in diabetic retinopathy and tumors, we hypothesized that insulin enhances intra-plaque angiogenesis. An in vitro model of pathological angiogenesis was used to assess the potential of insulin to enhance capillary-like tube formation of human microvascular endothelial cells (hMVEC) into a three dimensional fibrin matrix. In addition, insulin receptor expression within atherosclerotic plaques was visualized in carotid endarterectomy specimens of 20 patients with carotid artery stenosis, using immunohistochemical techniques. Furthermore, microvessel density within atherosclerotic plaques was compared between 68 DM2 patients who received insulin therapy and 97 DM2 patients who had been treated with oral glucose lowering agents only. Insulin, at a concentration of 10(-8)M, increased capillary-like tube formation of hMVEC 1.7-fold (p<0.01). Within human atherosclerotic plaques, we observed a specific distribution pattern for the insulin receptor...Continue Reading
References
Nov 1, 1979·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·L A Sternberger, S A Joseph
Feb 1, 1975·Circulation Research·R W StoutR Ross
Feb 1, 1981·Diabetologia·B Pfeifle, H Ditschuneit
Mar 1, 1996·The Journal of Cell Biology·P KoolwijkV W van Hinsbergh
Dec 1, 1995·Diabetes Care·M HenricssonL Groop
May 18, 1999·Microvascular Research·S YamagishiH Yamamoto
Oct 16, 2002·Diabetologia·M OkouchiM Itoh
Jun 19, 2003·The Journal of Clinical Investigation·Tatsuya KondoC Ronald Kahn
Feb 1, 2005·European Journal of Epidemiology·Bart A N VerhoevenGerard Pasterkamp
Aug 16, 2005·Endocrinology·Guolian LiZhenqi Liu
May 11, 2006·Circulation·Pedro R MorenoValentin Fuster
Oct 24, 2007·Journal of Vascular Surgery·Willem E HellingsFrans L Moll
Jan 10, 2008·Journal of Vascular Research·Simone PostAryan Vink
Jul 10, 2008·Pharmacoepidemiology and Drug Safety·David J MargolisBrian L Strom
Feb 5, 2009·Thrombosis and Haemostasis·Rosalinda Madonna, Raffaele De Caterina
Mar 25, 2009·The Journal of Pathology·Judith C Sluimer, Mat J Daemen
Aug 1, 2009·Ophthalmology·Claus CursiefenDaniel Meller
Oct 1, 2009·Diabetes, Obesity & Metabolism·J-M GambleJ A Johnson
Jan 30, 2010·Lancet·Craig J CurrieChris D Poole
Feb 26, 2010·Diabetologia·K L RensingJ H von der Thüsen
Apr 21, 2010·Circulation·Willem E HellingsGerard Pasterkamp
Oct 13, 2010·Diabetes Care·Danielle C ColaycoT Craig Cheetham
Citations
Sep 3, 2013·Diabetes Technology & Therapeutics·Caroline K Kramer, Bernard Zinman
Feb 19, 2013·Reviews in Endocrine & Metabolic Disorders·Etto C EringaVictor W M van Hinsbergh
Jan 1, 2014·Journal of Clinical Medicine·Yoshifumi Saisho
Mar 7, 2012·Atherosclerosis·Gisèle Clofent-SanchezJeanny Laroche-Traineau
Mar 6, 2012·Atherosclerosis·Sarah E Holden, Craig J Currie
Oct 9, 2018·International Journal of Clinical Practice·Marko SkelinDario Rahelić
Dec 29, 2019·Scientific Reports·Habtamu B DersehKen J Snibson
Aug 5, 2015·Current Opinion in Lipidology·Victor W M van HinsberghMat J A P Daemen
Mar 28, 2021·BMJ Open·Jeremiah HadwenMichel Shamy
Nov 9, 2021·Frontiers in Pharmacology·Habtamu B DersehKen J Snibson