PI3Kinases in Diabetes Mellitus and Its Related Complications

• Published in: International journal of molecular sciences Vol. 19; no. 12; p. 4098
• Main Authors: Maffei, Angelo, Lembo, Giuseppe, Carnevale, Daniela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.12.2018; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Ablation; Alzheimer Disease - complications; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Alzheimer's disease; Attention deficit hyperactivity disorder; Cardiomyopathies - genetics; Cardiomyopathies - physiopathology; Cardiomyopathy; Cell growth; Class Ib Phosphatidylinositol 3-Kinase - genetics; Class II Phosphatidylinositol 3-Kinases - genetics; Clinical trials; Congestive heart failure; Diabetes; Diabetes Complications - genetics; Diabetes Complications - physiopathology; Diabetes mellitus; Diabetes Mellitus - genetics; Diabetes Mellitus - physiopathology; Drug development; Drug therapy; Drugs; Enzymes; Glucose; Glucose - metabolism; Homeostasis; Humans; Insulin; Isoforms; Kinases; Lipids; Lymphoma; Metabolism; Nephropathy; Neurological diseases; Organs; Oxidative stress; pharmacological target; Phosphatidylinositol 3-Kinases - genetics; phosphoinositide 3-kinase; Phosphorylation; Proteins; Regulation; Review; Vascular diseases; diabetes mellitus; phosphoinositide 3-kinase; pharmacological target
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19124098

Recent studies have shown that phosphoinositide 3-kinases (PI3Ks) have become the target of many pharmacological treatments, both in clinical trials and in clinical practice. PI3Ks play an important role in glucose regulation, and this suggests their possible involvement in the onset of diabetes mellitus. In this review, we gather our knowledge regarding the effects of PI3K isoforms on glucose regulation in several organs and on the most clinically-relevant complications of diabetes mellitus, such as cardiomyopathy, vasculopathy, nephropathy, and neurological disease. For instance, PI3K α has been proven to be protective against diabetes-induced heart failure, while PI3K γ inhibition is protective against the disease onset. In vessels, PI3K γ can generate oxidative stress, while PI3K β inhibition is anti-thrombotic. Finally, we describe the role of PI3Ks in Alzheimer's disease and ADHD, discussing the relevance for diabetic patients. Given the high prevalence of diabetes mellitus, the multiple effects here described should be taken into account for the development and validation of drugs acting on PI3Ks.