Obesity-related changes in the vascular actions of insulin

• Main Authors: Francesca Schinzari, Manfredi Tesauro, Carmine Cardillo
• Format: Article
• Language: English
• Published: Elsevier 2021-03-01
• Series: Endocrine and Metabolic Science
• Subjects: Insulin; Endothelium; Obesity; Insulin resistance; Atherosclerosis
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666396120300297

Over the past 2 to 3 decades, research has focused on the changes in the vascular effects of insulin occurring in insulin resistant states like obesity. Consistent evidence indicates that obesity results in reduced endothelial release of nitric oxide in response to insulin, associated with concomitant enhancement in the production of endothelin-1. More recent work has pointed toward reduced vascular permeability and changes in the physical-chemical characteristics of the perivascular extracellular matrix as additional mechanisms of impaired insulin sensitivity in obesity. All these perturbations are important, because they contribute to impaired delivery of insulin itself and metabolic substrates to the target tissues and may play a role in the development of both diabetes and vascular damage. This review will describe the physiological vascular actions of insulin and their changes in obesity, focusing on some established pathophysiological determinants of the derangement of vascular insulin signaling, such as the lipid overflow from expanded fat depots and signals originating from inflamed obese adipose tissue (both distant and perivascular). Also, it will outline novel evidence underscoring the contribution of dysregulated adipokine secretion and changes in intestinal permeability and gut microbiome. Finally, it will touch upon some unresolved issues, such as the potential role of vascular insulin resistance in obesity-driven adipose tissue remodeling, and will discuss perspectives for future studies, regarding in particular possible therapeutic strategies with translational implications for the patients care.