Abstract
Diabetes and pre-diabetes are major contributors to cardiovascular mortality and morbidity. Insulin resistance is a key pathophysiological determinant of the metabolic and vascular abnormalities noted in these disorders. Ineffective vascular repair is likely to be an important contributor to the development of endothelial dysfunction, and subsequently atherosclerosis, in patients with diabetes. Beyond the systemic effects of the insulin resistant phenotype, including factors such as dysglycaemia and inflammation, cellular insulin resistance is emerging as an important factor in diabetic vascular disease. Disordered signal transduction via the PI3-kinase/Akt and MAP-kinase cascades is a hallmark of cellular insulin resistance, and such changes have been linked with both endothelial dysfunction and impaired angiogenesis. In this review we highlight the importance of insulin resistance to vascular repair and regeneration, discuss important cross-talk between the intracellular signalling of insulin and key pro-angiogenic molecules, and link these concepts to common patterns of vascular disease.
Keywords: Angiogenesis, diabetes, insulin resistance, insulin-like growth factor-1, progenitor, vascular
Current Vascular Pharmacology
Title:Insulin- and Growth Factor-Resistance Impairs Vascular Regeneration in Diabetes Mellitus
Volume: 10 Issue: 3
Author(s): Richard M. Cubbon, Noman Ali, Anshu Sengupta and Mark T. Kearney
Affiliation:
Keywords: Angiogenesis, diabetes, insulin resistance, insulin-like growth factor-1, progenitor, vascular
Abstract: Diabetes and pre-diabetes are major contributors to cardiovascular mortality and morbidity. Insulin resistance is a key pathophysiological determinant of the metabolic and vascular abnormalities noted in these disorders. Ineffective vascular repair is likely to be an important contributor to the development of endothelial dysfunction, and subsequently atherosclerosis, in patients with diabetes. Beyond the systemic effects of the insulin resistant phenotype, including factors such as dysglycaemia and inflammation, cellular insulin resistance is emerging as an important factor in diabetic vascular disease. Disordered signal transduction via the PI3-kinase/Akt and MAP-kinase cascades is a hallmark of cellular insulin resistance, and such changes have been linked with both endothelial dysfunction and impaired angiogenesis. In this review we highlight the importance of insulin resistance to vascular repair and regeneration, discuss important cross-talk between the intracellular signalling of insulin and key pro-angiogenic molecules, and link these concepts to common patterns of vascular disease.
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Cite this article as:
M. Cubbon Richard, Ali Noman, Sengupta Anshu and T. Kearney Mark, Insulin- and Growth Factor-Resistance Impairs Vascular Regeneration in Diabetes Mellitus, Current Vascular Pharmacology 2012; 10 (3) . https://dx.doi.org/10.2174/157016112799959305
DOI https://dx.doi.org/10.2174/157016112799959305 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
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