Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease
Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease
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DOI：
10.1152/ajpendo.00237.2004
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发表时间：
2004-12-01
影响因子：
5.1
通讯作者：
Sjöholm, Å
中科院分区：
文献类型：
--
作者：
Nyström, T;Gutniak, MK;Sjöholm, Å
GLP-1刺激胰岛素分泌，抑制胰高血糖素分泌，延缓胃排空，抑制小肠蠕动，这些都是抗糖尿病肽的作用。内皮功能障碍与胰岛素抵抗和2型糖尿病密切相关，并可能导致这种使人衰弱的疾病的血管病变。因此，同时影响内皮功能障碍和胰岛素抵抗的干预措施可能有助于提高2型糖尿病患者的生存率。研究GLP-1对2型糖尿病合并稳定型冠心病患者内皮功能和胰岛素敏感性（S-I）的影响：1)12例；2)10例内皮功能和S-I正常的健康人。在随机交叉研究中，受试者输注重组GLP-1或生理盐水。采用超声法测定肱动脉缺血后FMD内皮功能。S-I [in (10) (-4) dl.kg(-1)]。min(-1) /(muU/ml)]采用高胰岛素钳技术测定。在2型糖尿病患者中，GLP-1输注显著增加了肱动脉直径较基线FMD（%）的相对变化（3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05），但对S-I无显著影响（4.5 +/- 0.8 vs. 5.2 +/- 0.9, P = NS）。在健康受试者中，GLP-1输注既不影响FMD(%) （11.9 +/- 0.9 vs. 10.3 +/- 1.0%, P = NS）也不影响S-I （14.8 +/- 1.8 vs. 11.6 +/- 2.0, P = NS）。我们得出结论，GLP-1可改善2型糖尿病合并冠心病患者的内皮功能障碍，但不能改善胰岛素抵抗。GLP-1的这种有益血管作用增加了糖尿病治疗中有用的肽的另一个有益特性。
GLP-1 stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying, and inhibits small bowel motility, all actions contributing to the anti-diabetogenic peptide effect. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus and may cause the angiopathy typifying this debilitating disease. Therefore, interventions affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in type 2 diabetes patients. We investigated GLP-1's effect on endothelial function and insulin sensitivity (S-I) in two groups: 1) 12 type 2 diabetes patients with stable coronary artery disease and 2) 10 healthy subjects with normal endothelial function and S-I. Subjects underwent infusion of recombinant GLP-1 or saline in a random crossover study. Endothelial function was measured by postischemic FMD of brachial artery, using ultrasonography. S-I [in (10(-4) dl.kg(-1).min(-1))/(muU/ml)] was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetic subjects, GLP-1 infusion significantly increased relative changes in brachial artery diameter from baseline FMD(%) (3.1 +/- 0.6 vs. 6.6 +/- 1.0%, P < 0.05), with no significant effects on S-I (4.5 +/- 0.8 vs. 5.2 +/- 0.9, P = NS). In healthy subjects, GLP-1 infusion affected neither FMD(%) (11.9 +/- 0.9 vs. 10.3 +/- 1.0%, P = NS) nor S-I (14.8 +/- 1.8 vs. 11.6 +/- 2.0, P = NS). We conclude that GLP-1 improves endothelial dysfunction but not insulin resistance in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.