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Prediction of the effect on antihyperglycaemic action of sitagliptin by plasma active form glucagon-like peptide-1
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作者 Akifumi Kushiyama Takako Kikuchi +6 位作者 Kentaro Tanaka Tazu Tahara Toshiko Takao Yukiko Onishi Yoko Yoshida Shoji Kawazu Yasuhiko Iwamoto 《World Journal of Diabetes》 SCIE CAS 2016年第11期230-238,共9页
AIM: To investigate whether active glucagon-like peptide-1(GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus(GLP-1 FEST:UMIN000010645). METHODS: Seventy-six patients with... AIM: To investigate whether active glucagon-like peptide-1(GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus(GLP-1 FEST:UMIN000010645). METHODS: Seventy-six patients with type 2 diabetes, who had insufficient glycemic control [Hemoglobin A1c(Hb A1c) ≥ 7%] in spite of treatment with metformin and/or sulfonylurea, were included in the investigation. Patients were divided into three groups by tertiles of fasting plasma active GLP-1 level, before the administration of 50 mg sitagliptin. RESULTS: At baseline, body mass index, serum UA, insulin and HOMA-IR were higher in the high active GLP-1 group than in the other two groups. The high active GLP-1 group did not show any decline of Hb A1c(7.6% ± 1.4% to 7.5% ± 1.5%), whereas the middle and low groups indicated significant decline of Hb A1c(7.4 ± 0.7 to 6.8 ± 0.6 and 7.4 ± 1.2 to 6.9 ± 1.3, respectively) during six months. Only the low and middle groups showed a significant increment of active GLP-1, C-peptide level, a decreased log and proinsulin/insulin ratio after administration. In logistic analysis, the low or middle group is a significantexplanatory variable for an Hb A1 c decrease of ≥ 0.5%, and its odds ratio is 4.5(1.40-17.6)(P = 0.01) against the high active GLP-1 group. This remains independent when adjusted for Hb A1 c level before administration, patients' medical history, medications, insulin secretion and insulin resistance.CONCLUSION: Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin. 展开更多
关键词 dipeptidyl peptidase-4 inhibitor activE FORM glucagon-like peptide-1 Hemoglobin A1C Regression analysis
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牦牛乳酪蛋白肽分离组分对DPP-4活性的抑制作用 被引量:3
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作者 白函瑜 宋佳佳 +2 位作者 宋珏 王倩 毛学英 《食品科技》 CAS 北大核心 2015年第8期16-20,共5页
以牦牛乳酪蛋白为原料,研究牦牛乳酪蛋白水解产物及其分离组分对二肽基肽酶-4(DPP-4)活性的抑制作用。以木瓜蛋白酶水解牦牛乳酪蛋白,水解产物采用Sephadex G-25凝胶过滤色谱进行分离,以DPP-4抑制率为指标,分析水解产物和分离组分对DPP-... 以牦牛乳酪蛋白为原料,研究牦牛乳酪蛋白水解产物及其分离组分对二肽基肽酶-4(DPP-4)活性的抑制作用。以木瓜蛋白酶水解牦牛乳酪蛋白,水解产物采用Sephadex G-25凝胶过滤色谱进行分离,以DPP-4抑制率为指标,分析水解产物和分离组分对DPP-4活性的抑制作用。结果表明,木瓜蛋白酶水解0.5 h获得的水解产物表现出最强的DPP-4抑制活性,抑制率可达(59.57±0.23)%,半抑制浓度(IC50)为0.67 mg/m L。经Sephadex G-25凝胶过滤分离将木瓜蛋白酶水解产物分成4个组分,其中第3个组分对DPP-4抑制作用最强,IC50值为0.583 mg/m L。研究结果表明,与牦牛乳酪蛋白相比,其水解产物的DPP-4抑制活性显著增强,经凝胶过滤色谱分离后的水解产物分离组分具有更强的DPP-4抑制活性。 展开更多
关键词 牦牛乳 酪蛋白 水解产物 DPP-4抑制活性
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含尿嘧啶结构单元二肽衍生物的设计、合成及生物活性研究 被引量:1
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作者 唐雪梅 范莉 +1 位作者 张泽朝 杨大成 《有机化学》 SCIE CAS CSCD 北大核心 2019年第5期1460-1468,共9页
为探索新型抗糖尿病分子,设计了含有尿嘧啶结构单元的二肽衍生物.以尿嘧啶、多聚甲醛和半胱氨酸为原料,经过两步反应获得关键中间体S-胸腺嘧啶-L-半胱氨酸(IM-2),再经氨基保护、羧基酯化和氨基酸偶联,顺利合成了16个二肽衍生物.所得目... 为探索新型抗糖尿病分子,设计了含有尿嘧啶结构单元的二肽衍生物.以尿嘧啶、多聚甲醛和半胱氨酸为原料,经过两步反应获得关键中间体S-胸腺嘧啶-L-半胱氨酸(IM-2),再经氨基保护、羧基酯化和氨基酸偶联,顺利合成了16个二肽衍生物.所得目标化合物均经1H NMR、13C NMR和HRMS进行结构确认,并开展了过氧化物酶体增殖物受体反应元件(PPRE)激动活性、α-葡萄糖苷酶-rat抑制活性、二肽基肽酶-4(DPP-4)抑制活性筛选.生物活性结果显示,这些二肽衍生物的PPRE相对激动活性、α-葡萄糖苷酶和DPP-4抑制活性都很弱;同时发现,该类分子的α-葡萄糖苷酶抑制活性变化趋势与PPRE激动活性、DPP-4抑制活性变化趋势相反,这为新型多肽多靶点药物的设计提供了新思路. 展开更多
关键词 糖尿病 尿嘧啶 二肽衍生物 过氧化物酶体增殖物激活受体反应元件(PPRE) α-葡萄糖苷酶抑制活性 二肽基肽酶-4抑制活性
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