| IGF-I but not insulin inhibits apoptosis at a low concentration in vascular smooth muscle cells. | |
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MedLine Citation:
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PMID: 14596678 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apoptosis of vascular smooth muscle cells (VSMCs) is of importance in the development of diabetic angiopathy. Our aim was to evaluate the effect of insulin and IGF-I on apoptosis in VSMCs. Rat aortic VSMCs were used and apoptosis was induced by serum starvation. As apoptotic markers we measured caspase-3 activity, histone-associated DNA fragments by ELISA and nuclear morphology by DAPI (4',6-diamidino-2-phenylindole) staining. Phosphorylation of IGF-I receptors was evaluated by Western blot. Serum starvation had increased caspase-3 activity even after 3 h. The highest activity was found after 3-12 h. IGF-I 10(-9 )M inhibited serum starvation-induced caspase-3 activity with a maximal effect after 12 h. When studied after starvation for 12 h, significant inhibitory effects on caspase-3 were found at IGF-I concentrations of 10(-8)-10(-7) M (P<0.01) and at an insulin concentration of 10(-6 )M (P<0.01). DNA fragmentation was detected by ELISA after 24 h and chromatin condensation and nuclear fragmentation by DAPI staining after 24 and 48 h respectively. IGF-I dose-dependently reduced apoptosis evaluated by ELISA, reaching a maximal effect at 10(-9) M. Insulin reduced apoptosis but the effect was weaker and a higher concentration was needed. IGF-I (10(-8 )M) and insulin at a very high concentration (10(-6) M) phosphorylated IGF-I receptors. Taken together, IGF-I and insulin have antiapoptotic effects on VSMCs but the effect of insulin is only found at high unphysiological concentration. |
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Authors:
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R Jamali; M Bao; H J Arnqvist |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of endocrinology Volume: 179 ISSN: 0022-0795 ISO Abbreviation: J. Endocrinol. Publication Date: 2003 Nov |
Date Detail:
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Created Date: 2003-11-04 Completed Date: 2004-01-27 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0375363 Medline TA: J Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 267-74 Citation Subset: IM |
Affiliation:
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Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Linköping, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta Apoptosis / drug effects Blotting, Western / methods Caspase 3 Caspases / analysis Cells, Cultured Enzyme-Linked Immunosorbent Assay / methods Insulin / pharmacology* Insulin-Like Growth Factor I / pharmacology* Male Muscle, Smooth, Vascular / cytology*, drug effects, metabolism Phosphorylation Rats Rats, Sprague-Dawley Receptor, IGF Type 1 / metabolism |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor, IGF Type 1; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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