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Actions and interactions of insulin-like growth factor-I and insulin in vascular smooth muscle

Bornfeldt, Karin E., (författare)
Linköpings universitet, Farmakologi, Linköpings universitet, Internmedicin, Linköpings universitet, Hälsouniversitetet
Smith, Ulf, Professor (opponent)
Göteborg, Sverige
ISBN 91-7870-625-4
Linköping : Linköpings universitet, 1991
Engelska 65s.
Serie: Linköping University Medical Dissertations, 0345-0082
  • Doktorsavhandling (övrigt vetenskapligt)
Abstract Ämnesord
  • <p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p> <p>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.</p>





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