glucagon-like-peptide-1 and Coronary-Stenosis

Multiple factors regulate glucagon-like peptide-1 (GLP-1) secretion, but a group of apparently healthy subjects showed blunted responses of GLP-1 secretion in our previous study. In this study, we examined whether the reduction in GLP-1 secretory capacity is associated with increased extent of coronary artery stenosis in non-diabetic patients. Non-diabetic patients who were admitted for coronary angiography without a history of coronary interventions were enrolled. Coronary artery stenosis was quantified by Gensini score (GS), and GS ≥ 10 was used as an outcome variable based on its predictive value for cardiovascular events. The patients (mean age, 66.5 ± 8.8 years; 71% males, n = 173) underwent oral 75 g-glucose tolerant tests for determination of glucose, insulin and active GLP-1 levels. The area under the curve of plasma active GLP-1 (AUC-GLP-1) was determined as an index of GLP-1 secretory capacity. AUC-GLP-1 was not correlated with fasting glucose, AUC-glucose, serum lipids or indices of insulin sensitivity. In multivariate logistic regression analysis for GS ≥ 10, AUC-GLP-1 < median, age and hypertension were selected as explanatory variables, though fasting GLP-1 level was not selected. The findings suggest that reduction in GLP-1 secretory capacity is a novel independent risk factor of coronary stenosis.

Topics: Aged; Area Under Curve; Coronary Stenosis; Female; Glucagon-Like Peptide 1; Humans; Logistic Models; Male; Multivariate Analysis; Risk Factors

Enhancement of glucagon-like peptide-1 (GLP-1) reduces glucose levels and preserves pancreatic β-cell function, but its effect against restenosis is unknown.. We investigated the effect of subcutaneous injection of exenatide or local delivery of a recombinant adenovirus expressing GLP-1 (rAd-GLP-1) into carotid artery, in reducing the occurrence of restenosis following balloon injury. As a control, we inserted β-galactosidase cDNA in the same vector (rAd-βGAL). Otsuka Long-Evans Tokushima rats were assigned to three groups (n = 12 each): (1) normal saline plus rAd-βGAL delivery (NS + rAd-βGAL), (2) exenatide plus rAd-βGAL delivery (Exenatide + rAd-βGAL), and (3) normal saline plus rAd-GLP-1 delivery (NS + rAd-GLP-1). Normal saline or exenatide were administered subcutaneously from 1 week before to 2 weeks after carotid injury. After 3 weeks, the NS + rAd-βGAL group showed the highest intima-media ratio (IMR; 3.73 ± 0.90), the exenatide + rAd-βGAL treatment was the next highest (2.80 ± 0.51), and NS + rAd-GLP-1 treatment showed the lowest IMR (1.58 ± 0.48, P < 0.05 vs. others). The proliferation and migration of vascular smooth muscle cells and monocyte adhesion were decreased significantly after rAd-GLP-1 treatment, showing the same overall patterns as the IMR. In injured vessels, the apoptosis was greater and MMP2 expression was less in the NS + rAd-GLP-1 than in the exenatide or rAd-βGAL groups. In vitro expressions of matrix metalloproteinases-2 and monocyte chemoattractant protein-1 and nuclear factor-kappa-B-p65 translocation were decreased more in the NS + rAd-GLP-1 group than in the other two groups (all P < 0.05).. Direct GLP-1 overexpression showed better protection against restenosis after balloon injury via suppression of vascular smooth muscle cell migration, increased apoptosis, and decreased inflammatory processes than systemic exenatide treatment. This has potential therapeutic implications for treating macrovascular complications in diabetes.

Topics: Adenoviridae; Animals; Apoptosis; Carotid Artery Injuries; Carotid Artery, External; Cell Adhesion; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Stenosis; Diabetes Mellitus; Disease Models, Animal; Exenatide; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Glucagon-Like Peptide 1; Human Umbilical Vein Endothelial Cells; Hypoglycemic Agents; Incretins; Male; Matrix Metalloproteinase 2; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Peptides; Rats, Inbred OLETF; Transcription Factor RelA; Transfection; Venoms