The Role of PKM2 in Diabetic Microangiopathy

Chao Tu, Liangzhi Wang, Lan Wei Department of Internal Medicine, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213000, People’s Republic of ChinaCorrespondence: Lan Wei, Department of Internal Medicine, the Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 0519 68871132, Email weilan06082021@163.comAbstract: Diabetic microangiopathy is among the most common complications affecting patients with diabetes, and includes both diabetic retinopathy (DR) and diabetic nephropathy (DKD). Diabetic microangiopathy remains a persistent threat to the health and quality of life of affected patients. Mechanistically, the severity of DR and DKD is tied to mitochondrial and glucose metabolism abnormalities, with the activation of the glycolytic enzyme pyruvate kinase M2 (PKM2) contributing to mitochondrial and glomerular dysfunction, abnormal renal hemodynamics, and retinopathy. PKM2 can activate inflammatory bodies in macrophages to promote the release of inflammatory mediators, and serves as a key regulator of inflammatory factors, chemokines and adhesion molecules. As such, there is sufficient evidence that PKM2 can be used as a biomarker for the diagnosis of diabetes and diabetic microangiopathy. Here, we survey the mechanisms whereby PKM2 contributes to diabetes-related microvascular diseases, associated regulatory roles, post-translational modifications, and the potential utility of PKM2 as a therapeutic target. Through this literature review, we have determined that PKM2 offers promise as both a diagnostic marker and therapeutic target with direct relevance to research pertaining to diabetic microangiopathy.Keywords: pyruvate kinase M2, inflammation, diabetic retinopathy, diabetic nephropathy, diabetic microangiopathy