Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats
Treatment with DPP-4I Anagliptin or α-GI Miglitol Reduces IGT Development and the Expression of CVD Risk Factors in OLETF Rats
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DOI：
10.3177/jnsv.61.313
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发表时间：
2015-08-01
影响因子：
1.6
通讯作者：
Goda, Toshinao
中科院分区：
文献类型：
--
作者：
Imai, Chihiro;Harazaki, Tomomi;Goda, Toshinao
据报道，从糖尿病前期阶段，特别是从糖耐量受损（IGT）阶段开始的餐后高血糖与随后的心血管疾病（CVD）和2型糖尿病的发病率呈正相关。在这项研究中，我们的目的是研究是否与二肽基肽酶-4抑制剂（DPP-4 I）或α-葡萄糖苷酶抑制剂（α-GI），其中任何一种抑制餐后高血糖症，减少IGT动物模型中的CVD危险因素的表达。在IGT阶段，对自发性2型糖尿病模型Otsuka Long-Evans德岛脂肪（OLETF）大鼠给予饲料中的DPP-4 I（阿格列汀）（1，200 ppm）或α-GI（米格列醇）（600 ppm），持续47周。我们检查了每种治疗是否降低了CVD危险因素的表达，如外周血白细胞中的炎性细胞因子/趋化因子样因子以及主动脉组织和循环中的粘附分子。在第25周和第39周，任何一种药物治疗都能减少IGT的发生，并抑制空腹状态下外周血白细胞中白细胞介素-1 β、肿瘤坏死因子-α、S100 a9和S100 a11基因的表达。与对照组相比，阿格列汀和米格列醇组主动脉组织中E-选择素的mRNA水平以及动脉血中可溶性E-选择素和ICAM-1的蛋白水平均显著降低。我们的研究结果表明，在IGT阶段的OLETF大鼠中长期使用阿格列汀或米格列醇治疗可抑制外周血白细胞中炎性细胞因子和主动脉组织中粘附分子的表达。
It has been reported that postprandial hyperglycemia from the pre-diabetic stage, especially from the impaired glucose tolerance (IGT) stage, is positively associated with subsequent incidences of cardiovascular diseases (CVD) and type 2 diabetes. In this study, we aimed to investigate whether treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4I) or an alpha-glucosidase inhibitor (alpha-GI), either of which suppresses postprandial hyperglycemia, reduces the expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin (1,200 ppm), or an alpha-GI, miglitol (600 ppm), in the diet was administered for 47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether each treatment reduced the expression of CVD risk factors such as inflammatory cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules in the aortic tissues and circulation. Treatment with either drug reduced IGT development and repressed expression of the interleukin-1 beta, tumor necrosis factor-alpha, S100a9, and S100a11 genes in peripheral leukocytes in the fasting state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood were significantly lower in the anagliptin and miglitol groups than in the control group. Our results suggest that long-term treatment with anagliptin or miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory cytokines in peripheral leukocytes and adhesion molecules in aortic tissues.