Insulin resistance, cardiovascular stiffening and cardiovascular disease.
Animals
Cardiovascular Diseases
/ epidemiology
Endothelium, Vascular
/ metabolism
Humans
Immediate-Early Proteins
/ physiology
Insulin Resistance
/ genetics
Metabolic Syndrome
/ epidemiology
Nitric Oxide
/ metabolism
Protein Serine-Threonine Kinases
/ physiology
Signal Transduction
/ genetics
Vascular Stiffness
/ genetics
Cardiovascular disease
EnNaC
Insulin resistance
SGK-1
Vascular stiffness
Journal
Metabolism: clinical and experimental
ISSN: 1532-8600
Titre abrégé: Metabolism
Pays: United States
ID NLM: 0375267
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
22
12
2020
revised:
10
03
2021
accepted:
17
03
2021
pubmed:
27
3
2021
medline:
25
6
2021
entrez:
26
3
2021
Statut:
ppublish
Résumé
The cardiometabolic syndrome (CMS) and obesity are typically characterized by a state of metabolic insulin resistance. As global and US rates of obesity increase there is an acceleration of the incidence and prevalence of insulin resistance along with associated cardiovascular disease (CVD). Under physiological conditions insulin regulates glucose homeostasis by enhancing glucose disposal in insulin sensitive tissues while also regulating delivery of nutrients through its vasodilation actions on small feed arteries. Specifically, insulin-mediated production of nitric oxide (NO) from the vascular endothelium leads to increased blood flow enhancing disposal of glucose. Typically, insulin resistance is considered as a decrease in sensitivity or responsiveness to the metabolic actions of insulin including insulin-mediated glucose disposal. However, a decreased sensitivity to the normal vascular actions of insulin, especially diminished nitric oxide production, plays an additional important role in the development of CVD in states of insulin resistance. One mechanism by which insulin resistance and attendant hyperinsulinemia promote CVD is via increases in vascular stiffness. Although obesity and insulin resistance are known to be associated with substantial increases in the prevalence of vascular fibrosis and stiffness the mechanisms and mediators that underlie vascular stiffening in insulin resistant states are complex and have only recently begun to be addressed. Current evidence supports the role of increased plasma levels of aldosterone and insulin and attendant reductions in bioavailable NO in the pathogenesis of impaired vascular relaxation and vascular stiffness in the CMS and obesity. Aldosterone and insulin both increase the activity of serum and glucocorticoid kinase 1 (SGK-1) which in turn is a major regulator of vascular and renal sodium (Na
Identifiants
pubmed: 33766485
pii: S0026-0495(21)00066-4
doi: 10.1016/j.metabol.2021.154766
pii:
doi:
Substances chimiques
Immediate-Early Proteins
0
Nitric Oxide
31C4KY9ESH
Protein Serine-Threonine Kinases
EC 2.7.11.1
serum-glucocorticoid regulated kinase
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
154766Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The Authors have no conflicts of interest in regard to this manuscript.