Impact of hyperinsulinemia and hyperglycemia on valvular interstitial cells – A link between aortic heart valve degeneration and type 2 diabetes

Publication date: Available online 30 May 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Jessica I. Selig, D. Margriet Ouwens, Silja Raschke, G. Hege Thoresen, Jens W. Fischer, Artur Lichtenberg, Payam Akhyari, Mareike BarthAbstractType 2 diabetes is a known risk factor for cardiovascular diseases and is associated with an increased risk to develop aortic heart valve degeneration. Nevertheless, molecular mechanisms leading to the pathogenesis of valve degeneration in the context of diabetes are still not clear. Hence, we hypothesized that classical key factors of type 2 diabetes, hyperinsulinemia and hyperglycemia, may affect signaling, metabolism and degenerative processes of valvular interstitial cells (VIC), the main cell type of heart valves. Therefore, VIC were derived from sheep and were treated with hyperinsulinemia, hyperglycemia and the combination of both. The presence of insulin receptors was shown and insulin led to increased proliferation of the cells, whereas hyperglycemia alone showed no effect. Disturbed insulin response was shown by impaired insulin signaling, i.e. by decreased phosphorylation of Akt/GSK-3α/β pathway. Analysis of glucose transporter expression revealed absence of glucose transporter 4 with glucose transporter 1 being the predominantly expressed transporter. Glucose uptake was not impaired by disturbed insulin response, but was increased by hyperinsulinemia and was decreased by hyperglycemia. Analyses ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research