Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance

Figures

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  Fig. 1.. The signaling pathway of insulin action and the selective impairment of insulin receptor substrate (IRS)-protein kinase B (Akt) signaling pathway in insulin resistance. (A) It shows that insulin binding to the insulin receptor α subunit on the target cell surface activates the receptor subunit tyrosine kinase, leading to the autophosphorylation and phosphorylation of the IRS1/2, which activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and the RAS/mitogen-activated protein kinase (MAPK) pathway. (B) It shows that in insulin-resistant state, PI3K/Akt signaling is impaired, but the MAPK pathway is preserved, which may lead to a mitogenic-promoting effect of insulin in endothelial cells involved in vascular injury. GDP, guanosine 5´-diphosphate; GTP, guanosine 5´-triphosphate; PIP3, phosphatidylinositol 3,4,5-trisphosphate; GLUT-4, glucose transporter-4; RaF, rapidly accelerated fibrosarcoma; MEK, mitogen-activated protein kinase; PDPK1, phosphoinositide dependent protein kinase 1; ASC16, 6-O-ascorbyl palmitate ester; ERK, extracellular regulated kinase; eNOS, endothelial nitric oxide synthase; NF-κB, nuclear factor-κB; FoxO1, forkhead transcription factor O1; mTOR,…

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  Fig. 2.. Mechanisms of insulin resistance-induced diabetes heart disease (DHD). Insulin resistance affects the progression of DHD by altering cardiovascular risk factors and reducing the insulin signaling pathway, causing a number of cardiovascular diseases such as myocardial fibrosis, ventricular hypertrophy, atherosclerosis, impaired myocardial systolic and diastolic function, and hypertension. INS, insulinase-like proteases; NF-κB, nuclear factor-κB; NET, neutrophil extracellular trap; VSMC, vascular smooth muscle cells; GLUT-4, glucose transporter-4; CD36, cluster differentiation protein 36; FFA, free fatty acid; ROS, reactive oxygen species; ATP, adenosine triphosphate.