Diabetes Metab J.  2011 Oct;35(5):437-443. 10.4093/dmj.2011.35.5.437.

Understanding the Cardiovascular Effects of Incretin

• Yoon JS
• Lee HW

• KMID: 1857497
• DOI: http://doi.org/10.4093/dmj.2011.35.5.437

Abstract

Cardiovascular disease (CVD), a leading cause of death in patients with diabetes mellitus, has several pathogenic mechanisms that are well established. However, the traditional hypoglycemic agents do not have proven positive effects on macrovascular disease. Novel therapeutic agents target the incretin pathway including the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists and the dipeptidyl peptidase-4 inhibitors. The glucose-regulatory actions of these agents function by increasing insulin secretion and suppressing glucagon. They also act to increase weight loss not only by inhibiting gastric emptying, but also by reducing appetite. Although GLP-1 and GLP-1R agonists have demonstrated beneficial effects on myocardium and vascular endothelium including coronary and peripheral mouse vessels, they also have anti-inflammatory and anti-atherogenic actions. These agents also have positive effects on the lipid profile and blood pressure. Although these cardioprotective actions seem to be beyond the effects of glucose control and weight loss, they are mediated through GLP-1R- or GLP-1R-independent actions of cleaved GLP-1 (9-36). Larger randomized controlled trials are necessary to elucidate the clinical promise of these beneficial CVD effects.

Keyword

Cardiovascular diseases; Diabetes mellitus; Glucagon-like peptide 1; Incretins

MeSH Terms

Animals
Appetite
Blood Pressure
Cardiovascular Diseases
Cause of Death
Diabetes Mellitus
Endothelium, Vascular
Gastric Emptying
Glucagon
Glucagon-Like Peptide 1
Glucose
Humans
Hypoglycemic Agents
Incretins
Insulin
Mice
Myocardium
Weight Loss
Glucagon
Glucagon-Like Peptide 1
Glucose
Hypoglycemic Agents
Incretins
Insulin

Figure

• 

  Fig. 1 Exendin-4 reduced monocyte adhesion to the endothelium and atherosclerotic lesions in apoE-/- mice after 28-day treatment. (A) En face immunohistochemical staining of Mac-2 antibody of the aorta (n=7). (B) mRNA expression levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) (n=5-7). (C) Aortic sinuses stained with oil red O and the mean area of oil red O-positive lesions (n=20). Data are mean±SEM. aP<0.05 vs. control (Adapted from Arakawa M, et al. Diabetes 2010;59:1030-7) [26].

• 

  Fig. 2 Exenatide treatment after 75 minutes of coronary artery ligation and subsequent reperfusion in pigs. Myocardial infarct size quantification as a percentage of the area at risk (AAR) (A) and as a percentage of the total left ventricle (LV) (B). PBS (n=9); exenatide (n=9). Representative pictures after Evans blue and triphenyltetrazolium chloride (C, D). Blue indicates non-threatened myocardium, red indicates the noninfarcted area within the area at risk, and white indicates myocardial infarction. Quantifications of immunostaining for 8-hydroxydeoxy-guanosine (E) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay (F) (Adapted from Gill A, et al. Cardiovasc Diabetol 2010;9:6) [38].

• 

  Fig. 3 Physiological cardioprotective actions (A) and proposed mechanisms of glucagon-like peptide 1 (GLP-1) through a novel two-pathway (B). GLP-1R, GLP-1 receptor; DPP-4, dipeptidyl peptidase-4, BP, blood pressure (Modified from Mudaliar S, et al. Am J Med 2009;122(6 Suppl):S25-36, and Ban K, et al. J Am Soc Hypertens 2009;3:245-59. Used with permission) [31,43].

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