Sakata Shohei, Ito Makoto, Mera Yasuko, Sasase Tomohiko, Yamamoto Hiromi, Kakutani Makoto, Ohta Takeshi
Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
J Diabetes Res. 2014;2014:803832. doi: 10.1155/2014/803832. Epub 2014 May 7.
We investigated the effects of JTT-130 on glucose and lipid metabolism independent of the suppression of feeding by comparing with pair-fed animals. Male Zucker diabetic fatty (ZDF) rats were divided into control, JTT-130 treatment, and pair-fed groups. The rats were fed with a regular powdered diet with or without JTT-130 as a food admixture for 6 weeks. We compared the effects on glucose and lipid metabolism in JTT-130 treatment group with those in pair-fed group. RESULTS. Hyperglycemia in ZDF rats was prevented in both JTT-130 treatment and pair-fed groups, but the prevention in pair-fed group became poor with time. Moreover, reduction in plasma cholesterol levels was observed only in JTT-130 treatment group. JTT-130 treatment group showed improved glucose tolerance at 5 weeks after treatment and significant elevation of portal glucagon-like peptide-1 (GLP-1) levels. The hepatic lipid content in JTT-130 treatment group was decreased as compared with pair-fed group. Furthermore, pancreatic protection effects, such as an increase in pancreatic weight and an elevation of insulin-positive area in islets, were observed after JTT-130 treatment. CONCLUSIONS. JTT-130 improves hyperglycemia and dyslipidemia via a mechanism independent of suppression of food intake, which is ascribed to an enhancement of GLP-1 secretion and a reduction of lipotoxicity.
我们通过与配对喂养的动物进行比较，研究了JTT-130对葡萄糖和脂质代谢的影响，该影响独立于对进食的抑制作用。雄性Zucker糖尿病脂肪（ZDF）大鼠被分为对照组、JTT-130治疗组和配对喂养组。给大鼠喂食含有或不含有作为食物添加剂的JTT-130的常规粉状饲料，持续6周。我们比较了JTT-130治疗组和配对喂养组对葡萄糖和脂质代谢的影响。结果。JTT-130治疗组和配对喂养组均预防了ZDF大鼠的高血糖，但配对喂养组的预防效果随时间变差。此外，仅在JTT-130治疗组中观察到血浆胆固醇水平降低。JTT-130治疗组在治疗后5周显示出葡萄糖耐量改善，门静脉胰高血糖素样肽-1（GLP-1）水平显著升高。与配对喂养组相比，JTT-130治疗组的肝脏脂质含量降低。此外，JTT-130治疗后观察到胰腺保护作用，如胰腺重量增加和胰岛中胰岛素阳性面积升高。结论。JTT-130通过一种独立于抑制食物摄入的机制改善高血糖和血脂异常，这归因于GLP-1分泌的增强和脂毒性的降低。
