In vivo proliferation of rat vascular smooth muscle in relation to diabetes mellitus insulin-like growth factor I and insulin.
The roles of diabetes mellitus, insulin-like growth factor I and insulin in vascular smooth muscle proliferation in vivo were studied. Proliferation was induced by endothelial injury (balloon catheterization) of rat aorta, and was measured as 3H-thymidine incorporation into DNA. Levels of insulin-like growth factor I mRNA and insulin-like growth factor I receptor mRNA were measured with a solution hybridization assay. The increase in DNA synthesis was most pronounced 2 days after injury in both normal and diabetic rats and declined thereafter, but DNA synthesis in aortas from diabetic rats was lower throughout the time period studied. Levels of insulin-like growth factor I mRNA and the receptor mRNA were both increased in balloon catheterized aortas, and time-course studies showed an increase in receptor mRNA prior to the increase in insulin-like growth factor I mRNA. Diabetic rats were treated with equimolar concentrations of insulin (35 nmol/day) or insulin-like growth factor I (31 nmol/day) for 5 days. Insulin-like growth factor I increased DNA synthesis in injured aortas 2 days after injury without improving blood glucose, whereas the effect of insulin was associated with a decrease in blood glucose levels. In conclusion, vascular smooth muscle proliferation is impaired by diabetes and stimulated by insulin treatment. Insulin-like growth factor I infusion stimulates vascular smooth muscle proliferation without affecting blood glucose, and gene expressions of insulin-like growth factor I and its receptor are increased in proliferating vascular smooth muscle, indicating that insulin-like growth factor I and involved in vascular smooth muscle proliferation in vivo.
Bornfeldt
K E
KE
Department of Pharmacology, Linköping University, Faculty of Health Sciences, Sweden.
Arnqvist
H J
HJ
Capron
L
L
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D061389:Insulin, Regular, Pork; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D007328:Insulin; D061389:Insulin, Regular, Pork; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; C000006:insulin, neutral; D013936:Thymidine