title: In vivo effect of insulin to decrease matrix metalloproteinase-2 and -9 activity after arterial injury.
abstract: In vitro, insulin has both growth-promoting and vasculoprotective effects. In vivo, the effect of insulin is mainly protective. Insulin treatment (3 U/day) decreases smooth muscle cell (SMC) migration and neointimal growth after carotid angioplasty in normal rats maintained at normoglycemia by oral glucose. SMC migration requires limited proteolysis of the extracellular matrix, which is mediated by matrix metalloproteinases (MMPs). In this study, we investigated the effects of normoglycemic hyperinsulinemia on MMP activity after balloon angioplasty. Rats were divided into three groups: (1) control implants and tap water; (2) control implants and oral glucose, and (3) insulin implants (3 U/day) and oral glucose.
  
  
  RESULTS
  Gelatin zymography revealed that insulin reduced the gelatinolytic activity of pro-MMP-2 by 46% (p < 0.05), MMP-2 by 44% (p < 0.05) and MMP-9 by 51% (p < 0.05) compared to controls after arterial injury. Insulin also reduced mRNA levels of MMP-2 (p < 0.05) and MMP-9 (p < 0.05) and protein levels of MMP-2 (p < 0.05). In contrast, there were no significant changes in membrane-type 1 MMP protein and tissue inhibitors of MMP activity after insulin treatment. Thus, these results suggest a mechanism by which insulin inhibits SMC migration and supports a vasculoprotective role for insulin in vivo.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ont., Canada.
authors.forename: June
authors.initials: J
authors.lastname: Guo
authors.forename: Jiwanjeet K
authors.initials: JK
authors.lastname: Dhaliwall
authors.forename: Kalam K
authors.initials: KK
authors.lastname: Chan
authors.forename: Husam
authors.initials: H
authors.lastname: Ghanim
authors.forename: Nael
authors.initials: N
authors.lastname: Al Koudsi
authors.forename: Loretta
authors.initials: L
authors.lastname: Lam
authors.forename: Golnaz
authors.initials: G
authors.lastname: Madadi
authors.forename: Paresh
authors.initials: P
authors.lastname: Dandona
authors.forename: Adria
authors.initials: A
authors.lastname: Giacca
authors.forename: Michelle P
authors.initials: MP
authors.lastname: Bendeck
mesh_terms: D000284:Administration, Oral; D000800:Angioplasty, Balloon; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000201:enzymology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004343:Drug Implants; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D057772:Vascular System Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology
chemical_list: D001786:Blood Glucose; D004343:Drug Implants; D007328:Insulin; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D053511:Matrix Metalloproteinase 14; D005947:Glucose