Molecular Mechanisms by which a Grape Seed Procyanidin Extract Modulates Glucose Homeostasis

Abstract

Type 2 Diabetes is the most common form of diabetes and a prevalent health condition that resulted in 5.1 million deaths in 2013. Blood glucose levels are tightly regulated in order to maintain metabolic homeostasis. The hormone insulin, after binding to the insulin receptor, initiates a well-established controlled metabolic signaling cascade that consequently lowers blood glucose levels. There is considerable interest regarding effective natural therapies for combating glucose dysregulation. An example includes a grape seed procyanidin extract (GSPE), which has been demonstrated to decrease glucose levels in cell and animal models, however, the precise underlying molecular mechanisms are still under investigation. One of the reported mechanisms by which GSPE regulates glucose homeostasis is via action as an “insulinomimetic”, whereby, analogous to insulin, GSPE binds to the insulin receptor. Following binding to the insulin receptor, GSPE causes activation of the insulin signal transduction pathway, ultimately increasing glucose uptake. An additional mechanism by which GSPE is proposed to regulate blood glucose levels is via a direct effect on the primary glucose transporter in insulin-sensitive tissues, namely glucose transporter-4 (GLUT-4). The physiological effects of unregulated blood glucose and the detrimental health consequences will be discussed, along with currently available treatment strategies and potential future remedies in the field of medicine. The study of the literature presented in this thesis aims to provide evidence regarding the current knowledge base regarding the mechanisms identified thus far with respect to grape seed procyanidin extract and the regulation of glucose homeostasis.