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      Cardiovascular biology of the incretin system.

      1 ,
      Endocrine reviews
      The Endocrine Society

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          Abstract

          Glucagon-like peptide-1 (GLP-1) is an incretin hormone that enhances glucose-stimulated insulin secretion and exerts direct and indirect actions on the cardiovascular system. GLP-1 and its related incretin hormone, glucose-dependent insulinotropic polypeptide, are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4), a key determinant of incretin bioactivity. Two classes of medications that enhance incretin action, GLP-1 receptor (GLP-1R) agonists and DPP-4 inhibitors, are used for the treatment of type 2 diabetes mellitus. We review herein the cardiovascular biology of GLP-1R agonists and DPP-4 inhibitors, including direct and indirect effects on cardiomyocytes, blood vessels, adipocytes, the control of blood pressure, and postprandial lipoprotein secretion. Both GLP-1R activation and DPP-4 inhibition exert multiple cardioprotective actions in preclinical models of cardiovascular dysfunction, and short-term studies in human subjects appear to demonstrate modest yet beneficial actions on cardiac function in subjects with ischemic heart disease. Incretin-based agents control body weight, improve glycemic control with a low risk of hypoglycemia, decrease blood pressure, inhibit the secretion of intestinal chylomicrons, and reduce inflammation in preclinical studies. Nevertheless, there is limited information on the cardiovascular actions of these agents in patients with diabetes and established cardiovascular disease. Hence, a more complete understanding of the cardiovascular risk to benefit ratio of incretin-based therapies will require completion of long-term cardiovascular outcome studies currently underway in patients with type 2 diabetes mellitus.

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          Author and article information

          Journal
          Endocr Rev
          Endocrine reviews
          The Endocrine Society
          1945-7189
          0163-769X
          Apr 2012
          : 33
          : 2
          Affiliations
          [1 ] Department of Medicine, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada.
          Article
          er.2011-1052 CAMS2207
          10.1210/er.2011-1052
          3528785
          22323472
          5e44bfd3-a744-4ea1-977b-1ad9f8211180
          History

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