It is well recognized that insulin resistance found in patients with type 2 diabetes and obesity is a major risk factor for cardiovascular disease. Since its discovery in the 1920s, insulin has been used as an essential therapeutic agent in diabetes for blood glucose management. Recent studies demonstrate that insulin signalling is essential for normal cardiovascular function, and lack of it (i.e. insulin resistance) will result in cardiovascular dysfunction and disease. Moreover, insulin is the key component of glucose-insulin-potassium cocktail and exerts significant cardiovascular protective effect via a phosphatidylinositol 3'-kinase-protein kinase B-endothelial nitric oxide synthase (PI3K-Akt-eNOS)-dependent signalling mechanism in addition to its metabolic modulation, which renders it a potent organ protector in multiple clinical applications. This review focuses on insulin-initiated PI3K-Akt-eNOS survival signalling, with nitric oxide as an 'end effector' delivering cardioprotection in health and disease (especially in ischaemic heart disease), and highlights the impairment of this survival signalling as a key link between insulin resistance and cardiovascular disease.
Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction
Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium
Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells
Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats
Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione
Nitric oxide suppression of apoptosis occurs in association with an inhibition of Bcl-2 cleavage and cytochrome c release.
Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death
Biochemical characterization of S-nitrosohemoglobin. Mechanisms underlying synthesis, no release, and biological activity.
Glucose-insulin-potassium preserves systolic and diastolic function in ischemia and reperfusion in pigs
Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells
Nitric oxide down-regulates MKP-3 mRNA levels: involvement in endothelial cell protection from apoptosis
Increased sensitivity of mitochondrial respiration to inhibition by nitric oxide in cardiac hypertrophy
Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience
Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179)
In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone
Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling
p38 MAPK inhibition reduces myocardial reperfusion injury via inhibition of endothelial adhesion molecule expression and blockade of PMN accumulation
Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size
Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells
Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells
Attenuation of myocardial ischemia/reperfusion injury in mice with myocyte-specific overexpression of endothelial nitric oxide synthase
Nitric oxide, superoxide, and peroxynitrite in myocardial ischaemia-reperfusion injury and preconditioning
Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase
Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction. A preliminary clinical report
Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance
Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction
Images in cardiovascular medicine. Avoiding papillary muscle infarction with myocardial contrast echocardiographic guidance of nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy
The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction.
Cardiovascular consequences of sleep-disordered breathing: past, present and future: report of a workshop from the National Center on Sleep Disorders Research and the National Heart, Lung, and Blood Institute
Does oestradiol attenuate the damaging effects of a fructose-rich diet on cardiac Akt/endothelial nitric oxide synthase signalling?
Short-chain fatty acid propionate alleviates Akt2 knockout-induced myocardial contractile dysfunction
Propionyl-L-carnitine corrects metabolic and cardiovascular alterations in diet-induced obese mice and improves liver respiratory chain activity
Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis
Genetic variants in PCSK1 gene are associated with the risk of coronary artery disease in type 2 diabetes in a Chinese Han population: a case control study
Baicalin protects the cardiomyocytes from ER stress-induced apoptosis: inhibition of CHOP through induction of endothelial nitric oxide synthase
Achyranthes bidentata polypeptides reduces oxidative stress and exerts protective effects against myocardial ischemic/reperfusion injury in rats
Effective glycaemic control critically determines insulin cardioprotection against ischaemia/reperfusion injury in anaesthetized dogs
Insulin protects H9c2 rat cardiomyoblast cells against hydrogen peroxide-induced injury through upregulation of microRNA-210
Insulin inhibits inflammation and promotes atherosclerotic plaque stability via PI3K-Akt pathway activation
Mitochondrial JNK activation triggers autophagy and apoptosis and aggravates myocardial injury following ischemia/reperfusion
Obesity induced by high fat diet attenuates postinfarct myocardial remodeling and dysfunction in adult B6D2F1 mice
Dietary nitrite attenuates oxidative stress and activates antioxidant genes in rat heart during hypobaric hypoxia
p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-uncoupling in obesity.
Membrane receptor-dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia-reperfusion injury: in vivo and in vitro studies
Influence of feeding and intracoronary dose on insulin-mediated relative akt phosphorylation in the porcine myocardium
Overnourishment during lactation induces metabolic and haemodynamic heart impairment during adulthood
Insulin inhibits lipopolysaccharide-induced nitric oxide synthase expression in rat primary astrocytes
The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells
Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance
Relationships among protein tyrosine phosphatase 1B, angiotensin II, and insulin-mediated aortic responses in type 2 diabetic Goto-Kakizaki rats
Protective effects of coenzyme Q10 against angiotensin II-induced oxidative stress in human umbilical vein endothelial cells
Preclinical characterization of recombinant human tissue kallikrein-1 as a novel treatment for type 2 diabetes mellitus
mTOR-Independent autophagy inducer trehalose rescues against insulin resistance-induced myocardial contractile anomalies: Role of p38 MAPK and Foxo1
TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice
First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas
Disturbed nitric oxide and homocysteine production are involved in the increased risk of cardiovascular diseases in the F1 offspring of maternal obesity and malnutrition
Imbalanced Insulin Actions in Obesity and Type 2 Diabetes: Key Mouse Models of Insulin Signaling Pathway
Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure
Hydromorphine postconditioning protects isolated rat heart against ischemia-reperfusion injury via activating P13K/Akt/eNOS signaling
Cardiovascular Disease Pathophysiology
Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.
CV Disorders & Type 2 Diabetes
This feed focuses on the association of cardiovascular diseases in patients with type 2 diabetes.