Abstract
The underlying molecular mechanisms involve in the regulation of the angiogenic process by insulin are not well understood. In this review article, we aim to describe the role of insulin and insulin receptor activation on the control of angiogenesis and how these mechanisms can be deregulated in human diseases. Functional expression of insulin receptors and their signaling pathways has been described on endothelial cells and pericytes, both of the main cells involved in vessel formation and maturation. Consequently, insulin has been shown to regulate endothelial cell migration, proliferation, and in vitro tubular structure formation through binding to its receptors and activation of intracellular phosphorylation cascades. Furthermore, insulin-mediated pro-angiogenic state is potentiated by generation of vascular growth factors, such as the vascular endothelial growth factor, produced by endothelial cells. Additionally, diseases such as insulin resistance, obesity, diabetes, and cancer may be associated with the deregulation of insulin-mediated angiogenesis. Despite this knowledge, the underlying molecular mechanisms need to be elucidated in order to provide new insights into the role of insulin on angiogenesis.
Highlights
Insulin receptor(s) stimulation has pleiotropic effects on endothelial cells (Westermeier et al, 2011)
As a hormone involved in tissue growth and recovery after injury, is involved in the control of angiogenesis through at least four mechanisms reviewed in this article: (1) control of the interaction between endothelium and pericytes; (2) endothelial cell migration and proliferation; (3) synthesis of pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and Ang; and (4) regulation of tissue metabolism, which indirectly affects endothelial cell survival
Despite the fact that these effects are well described in the literature, the underling signaling pathways are not entirely known
Summary
Insulin receptor(s) stimulation has pleiotropic effects on endothelial cells (Westermeier et al, 2011). Insulin induces vasorelaxation, enhances endothelial uptake of amino acids (such as L-arginine) and increases survival and migration of endothelial cells (Dubó et al, 2016; Sobrevia et al, 2016). These actions, combined with the capacity of insulin to enhance expression of proangiogenic factors such as vascular endothelial growth factor (VEGF), as well as increase pericytes survival and reduce anti-angiogenic protein expression, have established the role of insulin in physiological and pathological angiogenesis (He et al, 2006). Angiogenesis is beneficial for tissue growth and regeneration, and it can enhance inflammatory response or malignant diseases; or can contribute to cancer metastasis leading to mortality (Cumsille et al, 2015)
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