Activation of Protein Kinase C Isoforms & Its Impact on Diabetic Complications
By P. Geraldes, G. King. Circulation Research, 2010
942 citations recorded by the source corpus.
Both cardio- and microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. Cardiovascular pathologies of diabetes have an effect on microvenules, arteries, and myocardium. It is believed that hyperglycemia is one of the most important metabolic factors in the development of both micro- and macrovascular complications in diabetic patients. Several prominent hypotheses exist to explain the adverse effect of hyperglycemia. One of them is the chronic activation by hyperglycemia of protein kinase C (PKC), a family of enzymes that are involved in controlling the function of other proteins. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC-α, -β1/2, and PKC-δ) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKC-β isoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy and endothelial dysfunction. This paper reviews current understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes.
Subfields: Endocrinology, Diabetes and Metabolism, Molecular Biology, Nephrology
View Paper: https://www.semanticscholar.org/paper/00d56340fc342e8d3ce5413f8212f6e2609ac0df
Citations in the corpus
- Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I (2013, neutral): “including alterations in cellular permeability, inflammation, angiogenesis, cell growth, extracellular matrix expansion, and apoptosis.(14) An”
- Mechanisms of diabetic complications. (2013, neutral): “Seminal studies by the Joslin group (201, 327, 328) and others (382) have emphasized the central role of PKC- in particular PKC- I and - II, in various diabetic complications including nephropathy, retinopathy, and cardiac dysfunction (384, 572, 627).”
- Vascular complications of diabetes: mechanisms of injury and protective factors (2013, neutral): “Abbreviations (see also Figure 3) are as follows: eNOS, endothelial nitric oxide synthase; ET-1, endothelin-1; FFA, free fatty acids; HO-1, heme oxygenase-1; INSR, insulin receptor; IRS, insulin receptor substrate; TNF-a, tumor necrosis factor a; VCAM-1, vascular cell adhesion molecule 1.”