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微粒体甘油三酯转移蛋白肠道特异性抑制剂与过氧化物酶体增殖物激活受体γ激动剂联合治疗糖尿病大鼠

Combination therapy of an intestine-specific inhibitor of microsomal triglyceride transfer protein and peroxisome proliferator-activated receptor γ agonist in diabetic rat.

作者信息

Sakata Shohei, Mera Yasuko, Kuroki Yukiharu, Nashida Reiko, Kakutani Makoto, Ohta Takeshi

机构信息

Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.

出版信息

J Diabetes Res. 2014;2014:890639. doi: 10.1155/2014/890639. Epub 2014 Mar 17.

DOI:10.1155/2014/890639
PMID:24772450
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3977080/
Abstract

We investigated effects on glucose and lipid metabolism in combination of JTT-130, a novel intestine-specific microsomal triglyceride transfer protein (MTP) inhibitor, and pioglitazone, peroxisome proliferator-activated receptor (PPAR) γ agonist. Male Zucker diabetic fatty rats were divided into 4 groups: control group, JTT-130 treatment group, pioglitazone treatment group, and combination group. The Zucker diabetic fatty rats were fed a regular powdered diet with JTT-130 and/or pioglitazone as a food admixture for 6 weeks. Effects on glucose and lipid metabolism were compared mainly between JTT-130 treatment group and combination group. JTT-130 treatment showed good glycemic control, while the plasma glucose and glycated hemoglobin levels in combination group were significantly decreased as compared with those JTT-130 treatment group. The reduction in the plasma triglyceride and free fatty acid levels in combination group was higher than that in JTT-130 treatment group, and glucose utilization was significantly elevated in adipose tissues. In Zucker diabetic fatty rats, combination treatment of JTT-130 and pioglitazone showed better glycemic control and a strong hypolipidemic action with an enhancement of insulin sensitivity. Combination therapy of MTP inhibitor and PPAR γ agonist might be more useful in the treatment of type 2 diabetes accompanied with obesity and insulin resistance.

摘要

我们研究了新型肠特异性微粒体甘油三酯转运蛋白（MTP）抑制剂JTT-130与过氧化物酶体增殖物激活受体（PPAR）γ激动剂吡格列酮联合使用对葡萄糖和脂质代谢的影响。雄性Zucker糖尿病脂肪大鼠被分为4组：对照组、JTT-130治疗组、吡格列酮治疗组和联合治疗组。给Zucker糖尿病脂肪大鼠喂食添加有JTT-130和/或吡格列酮的常规粉状饲料6周。主要比较JTT-130治疗组和联合治疗组对葡萄糖和脂质代谢的影响。JTT-130治疗显示出良好的血糖控制，而联合治疗组的血浆葡萄糖和糖化血红蛋白水平与JTT-130治疗组相比显著降低。联合治疗组的血浆甘油三酯和游离脂肪酸水平的降低高于JTT-130治疗组，并且脂肪组织中的葡萄糖利用率显著提高。在Zucker糖尿病脂肪大鼠中，JTT-130和吡格列酮联合治疗显示出更好的血糖控制和强大的降血脂作用，并增强了胰岛素敏感性。MTP抑制剂和PPARγ激动剂联合治疗可能在治疗伴有肥胖和胰岛素抵抗的2型糖尿病中更有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/ab79b1bf73ba/JDR2014-890639.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/4313424fae5f/JDR2014-890639.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/08737a8d8387/JDR2014-890639.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/c0830b8b947e/JDR2014-890639.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/ab79b1bf73ba/JDR2014-890639.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/4313424fae5f/JDR2014-890639.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/08737a8d8387/JDR2014-890639.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/c0830b8b947e/JDR2014-890639.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e887/3977080/ab79b1bf73ba/JDR2014-890639.004.jpg

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Expert Opin Pharmacother. 2011 Jul;12(10):1571-84. doi: 10.1517/14656566.2011.567266. Epub 2011 Jun 4.
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Type 2 diabetes can be prevented with early pharmacological intervention.2 型糖尿病可以通过早期药物干预来预防。
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