Actions and interactions of insulin-like growth factor-I and insulin in vascular smooth muscle
1991 (English)Doctoral thesis, comprehensive summary (Other academic)
Insulin-like growth factor-I (IGF-I) is a polypeptide with structural and biological similarities with insulin, and the receptors for IGF-I and insulin are homologous. The present investigation was devoted to the actions and interactions of IGF-I and insulin in vascular smooth muscle.
In vascular smooth muscle from intact arteries and in cultured vascular smooth muscle cells there are abundant IGF-I receptors, but very few insulin receptors. IGF-I and insulin stimulated proliferation of cultured vascular smooth muscle cells, and the effects were probably mediated via the IGF-I receptor. However, the maximal growthpromoting effect of IGF-I was twice the maximal effect of insulin. If an acidic amino acid was substituted for the basic amino acid histidine in insulin B-chain (BlO His:::} Asp), like in IGF-I, the maximal growth-promoting activity reached the effect of IGF-1. The amino acid in position 10 in insulin B-chain may thus be important for the growthpromoting activity of insulin.
Vascular smooth muscle cells express IGF-1 mRNA and produce imm1,1noreactive IGF-1 in vitro. Levels of IGF-1 m RNA were decreased by platelet-derived growth factor (PDGF-BB), basic fibroblast growth factor (bFGF) and serum, whereas IGF-1 and high concentrations of insulin increased IGF-I rnRNA and immunoreactive IGF-I. It is thus possible that IGF-1 is able to increase its own production in an autocrine loop withpositive feedback. The growth-promoting effects of IGF-1 and insulin were weak compared to the effects ofPDGF-BB and bFGF. The results indicate qualitative as well as quantitative differences between IGF-1 and insulin compared to PDGF-BB and bFGF.
IGF-1 gene expression in aortic tissue was found to be decreased by diabetes and fasting in vivo, and the levels were restored if diabetic rats were treated with insulin.
Vascular smooth muscle proliferation induced by balloon catheterization was found to be impaired by diabetes and increased by insulin-treatment in vivo, although not to the levels in normal rats. IGF-1 stimulated vascular smooth muscle proliferation in diabetic rats in vivo without affecting the diabetic state, and IGF-I gene expression was increased in proliferating vascular smooth muscle. The results suggest that IGF-I is involved in vascular smooth muscle proliferation in vivo.
In conclusion, insulin is less potent than IGF-1 in stimulating proliferation of vascular smooth muscle, and the growth-promoting effects of insulin are weaker than the effects ofiGF-1, suggesting that insulin in concentrations found in plasma has little direct effect on vascular smooth muscle proliferation. IGF-1 is probably of importance for vascular smooth muscle proliferation, and the results suggest that IGF-1 can be locally produced and regulated in the vascular wall.
Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1991. , 65 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 334
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-27466Local ID: 12119ISBN: 91-7870-625-4OAI: oai:DiVA.org:liu-27466DiVA: diva2:248018
1991-05-17, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Smith, Ulf, Professor
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.2009-10-082009-10-082012-07-18Bibliographically approved