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Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance
The effect of enhancing insulin’s actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001189/ https://www.ncbi.nlm.nih.gov/pubmed/27217486 http://dx.doi.org/10.2337/db15-1721 |
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author | Katagiri, Sayaka Park, Kyoungmin Maeda, Yasutaka Rao, Tata Nageswara Khamaisi, Mogher Li, Qian Yokomizo, Hisashi Mima, Akira Lancerotto, Luca Wagers, Amy Orgill, Dennis P. King, George L. |
author_facet | Katagiri, Sayaka Park, Kyoungmin Maeda, Yasutaka Rao, Tata Nageswara Khamaisi, Mogher Li, Qian Yokomizo, Hisashi Mima, Akira Lancerotto, Luca Wagers, Amy Orgill, Dennis P. King, George L. |
author_sort | Katagiri, Sayaka |
collection | PubMed |
description | The effect of enhancing insulin’s actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet–induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice. Increased angioblasts and EC numbers in GT of ECIRS1 mice were due to proliferation in situ rather than uptake. GT in HF-fed diabetic mice exhibited parallel decreases in insulin and VEGF-induced pAkt and EC numbers by >50% without changes in angioblasts versus WT mice, which were improved in ECIRS1 TG mice on normal chow or HF diet. Thus, HF-induced diabetes impaired angiogenesis by inhibiting insulin signaling in GT to decrease the differentiation of angioblasts to EC, which was normalized by enhancing insulin’s action targeted to EC, a potential target to improve wound healing in diabetes and obesity. |
format | Online Article Text |
id | pubmed-5001189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-50011892017-09-01 Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance Katagiri, Sayaka Park, Kyoungmin Maeda, Yasutaka Rao, Tata Nageswara Khamaisi, Mogher Li, Qian Yokomizo, Hisashi Mima, Akira Lancerotto, Luca Wagers, Amy Orgill, Dennis P. King, George L. Diabetes Complications The effect of enhancing insulin’s actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet–induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice. Increased angioblasts and EC numbers in GT of ECIRS1 mice were due to proliferation in situ rather than uptake. GT in HF-fed diabetic mice exhibited parallel decreases in insulin and VEGF-induced pAkt and EC numbers by >50% without changes in angioblasts versus WT mice, which were improved in ECIRS1 TG mice on normal chow or HF diet. Thus, HF-induced diabetes impaired angiogenesis by inhibiting insulin signaling in GT to decrease the differentiation of angioblasts to EC, which was normalized by enhancing insulin’s action targeted to EC, a potential target to improve wound healing in diabetes and obesity. American Diabetes Association 2016-09 2016-05-23 /pmc/articles/PMC5001189/ /pubmed/27217486 http://dx.doi.org/10.2337/db15-1721 Text en © 2016 by the American Diabetes Association. http://diabetesjournals.org/site/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://diabetesjournals.org/site/license. |
spellingShingle | Complications Katagiri, Sayaka Park, Kyoungmin Maeda, Yasutaka Rao, Tata Nageswara Khamaisi, Mogher Li, Qian Yokomizo, Hisashi Mima, Akira Lancerotto, Luca Wagers, Amy Orgill, Dennis P. King, George L. Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance |
title | Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance |
title_full | Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance |
title_fullStr | Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance |
title_full_unstemmed | Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance |
title_short | Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance |
title_sort | overexpressing irs1 in endothelial cells enhances angioblast differentiation and wound healing in diabetes and insulin resistance |
topic | Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001189/ https://www.ncbi.nlm.nih.gov/pubmed/27217486 http://dx.doi.org/10.2337/db15-1721 |
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