Glucagon Like Peptide-1 and Atherosclerosis

Tomoya      Mita; Hirotaka      Watada

Abstract

Patients with type 2 diabetes mellitus are at high risk for developing cardiovascular diseases. Traditional medicines for type 2 diabetes, such as sulfonylureas, pioglitazone, and insulin have glucose lowering effects; however, they also increase the frequency of hypoglycemia and/or body weight and thus may cancel out the benefits of glucose lowering on the development of atherosclerosis. In contrast, the recently developed glucagon like peptide-1-based therapy using glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors has numerous beneficial effects in the management of hyperglycemia with less risk of hypoglycemia and weight gain. Glucagon-like peptide-1-based therapy also lowers blood pressure and blood lipids and thus may prevent progression of atherosclerosis. Furthermore, glucagonlike peptide-1 receptors are abundantly expressed in vascular cells such as endothelial cells, monocyte/macrophages and smooth muscle cells. Recent studies suggest that the anti-inflammatory and vasodilatory properties of glucagon-like peptide-1 signaling on endothelial cells, its anti-inflammatory effect on macrophages and anti-proliferative effects on smooth muscle cells may halt atherosclerosis. Although large clinical trials are required to confirm these beneficial effects, glucagon-like peptide-1-based therapy could provide both glucose lowering and protection against cardiovascular diseases in patients with type 2 diabetes.

Keywords: Atherosclerosis, diabetes, endothelial cells, glucagon-like peptide-1, macrophage/monocyte, smooth muscle cells

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