Association of Protein Kinase B (AKT) DNA Hypermethylation with Maintenance Atypical Antipsychotic Treatment in Patients with Bipolar Disorder

Pharmacotherapy
Kyle J BurghardtZhengping Yi

Abstract

Atypical antipsychotics cause insulin resistance that leads to an increased risk of diabetes mellitus and cardiovascular disease. Skeletal muscle is the primary tissue for uptake of glucose, and its dysfunction is considered one of the primary defects in the development of insulin resistance. Protein kinase B (AKT) plays an important role in overall skeletal muscle health and glucose uptake into the muscle. The objective of this study was to measure AKT isoform-specific gene methylation differences in the skeletal muscle of patients with bipolar disorder treated with atypical antipsychotic or mood stabilizer maintenance therapy. Cross-sectional observational study. Clinical research services center at an academic center. Thirty patients with a confirmed diagnosis of bipolar disorder who were treated with either an atypical antipsychotic (16 patients) or mood stabilizer (14 patients) at a consistent dose for at least 3 months. A fasting skeletal muscle biopsy was performed in the vastus lateralis in each patient. Patients also underwent fasting blood sample collection and a standard 75-g oral glucose tolerance test. Skeletal muscle DNA methylation near the promoter region for three genes, AKT1, AKT2, and AKT3, was measured by me...Continue Reading

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