School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, UK.
Diabetes Obes Metab. 2018 Feb;20(2):319-327. doi: 10.1111/dom.13068. Epub 2017 Aug 22.
To investigate the chronic effects of twice-daily administration of stable apelin analogues, apelin-13 amide and pyroglutamyl (pGlu) apelin-13 amide, on metabolic variables in glucose-intolerant and insulin-resistant diet-induced obese mice fed a high-fat diet for 150 days.
Groups of mice received twice-daily (9 am and 5 pm) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1-39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity, together with pancreatic hormone content and biochemical variables such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry analysis and indirect calorimetry were also performed.
Administration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased body weight, food intake and blood glucose and increased plasma insulin compared with high-fat-fed saline-treated controls (P < .05 and P < .001), Additionally, all peptide-treated groups exhibited improved glucose tolerance (oral and intraperitoneal), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved glycated haemoglobin and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio, whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased glucagon-like peptide-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL cholesterol and total body fat, and increased pancreatic insulin content.
These data indicate the therapeutic potential of stable apelin-13 analogues, with effects equivalent to or better than those of exendin-4.
研究每日两次给予稳定型 Apelin 类似物 Apelin-13 酰胺和焦谷氨酸（pGlu）Apelin-13 酰胺对喂食高脂肪饮食 150 天的葡萄糖耐量受损和胰岛素抵抗的饮食诱导肥胖小鼠代谢变量的慢性影响。
将小鼠分为盐水对照组、Apelin-13 酰胺组、（pGlu）Apelin-13 酰胺组或 Exendin-4（1-39）组，每组接受每日两次（9 点和 5 点）注射，持续 28 天（均为 25nmol/kg）。监测能量摄入、体重、非空腹血糖、血浆胰岛素、葡萄糖耐量、进食代谢反应和胰岛素敏感性，以及胰腺激素含量和血脂等生化变量和总 GLP-1。还进行了双能 X 射线吸收法分析和间接量热法分析。
与高脂肪喂养的盐水对照组相比，Apelin-13 酰胺、（pGlu）Apelin-13 酰胺或 Exendin-4 给药显著降低了体重、食物摄入和血糖，增加了血浆胰岛素（P<.05 和 P<.001）。此外，所有肽处理组均表现出改善的葡萄糖耐量（口服和腹腔内）、进食代谢反应和相关胰岛素分泌。（pGlu）Apelin-13 酰胺在 28 天后还显著改善糖化血红蛋白和胰岛素敏感性。（pGlu）Apelin-13 酰胺和 Exendin-4 均增加了骨矿物质含量并降低了呼吸交换率，而只有（pGlu）Apelin-13 酰胺增加了能量消耗。所有治疗组均显示循环甘油三酯降低和胰高血糖素样肽-1 浓度增加，尽管只有（pGlu）Apelin-13 酰胺显著降低 LDL 胆固醇和总体脂肪，增加胰腺胰岛素含量。
这些数据表明稳定型 Apelin-13 类似物具有治疗潜力，其作用与 Exendin-4 相当或更好。
