Wang Haiyan, Qin Lingling, Wang Dongchao, Jiang Yueying, Wu Xinli, Xu Tunhai, Liu Tonghua, Li Linyi
Health-cultivation Laboratory of the Ministry of Education, Beijing University of Chinese Medicine, Beijing 100029, China.
Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
J Tradit Chin Med. 2017 Oct;37(5):588-598.
To assess the effect of a mixture of five herbal extracts (FT-5) on insulin resistance, glucose/lipid metabolism, hepatic steatosis, and to investigate whether the combination of FT-5 and pioglitazone would provide a robust effect on diabetes treatment, while may minimize undesirable side-effects of pioglitazone in diabetic Ay gene (KKAy) mice.
Seven-week-old KKAy mice were randomly divided into five groups: control (CON) group, FT-5 (2.0 g/kg) group, pioglitazone (20 mg/kg) (PIO) group, pioglitazone (20 mg/kg) + FT-5 (2.0 g/kg) (P + F) group. Age-matched C57BL/6J mice were used as the control group. After seven weeks of continuous intragastric administration of medication, the glucose metabolism, insulin sensitivity and lipid metabolism of KKAy mice were evaluated by assessing the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), fasting serum insulin (FINS), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index (HOMA-IR), total cholesterol (TC), total triglycerides (TG), and free fatty acids (FFA) in plasma and liver. Plasma and hepatic adiponectin were measured via enzyme-linked immunosorbent assays. Genes related to adipogenesis and lipolysis in white adipose tissues (WAT) and liver were examined by real-time polymerase chain reaction. Lipid metabolism-related protein expression in the liver of KKAy mice were detected by Western blotting.
PIO treatment remarkably improved insulin resistance. However, it also showed substantial side effects. FT-5 group exhibited no significant decrease in serum glucose. However, it reduced fasting plasma TG levels and improved hepatic steatosis of KKAy mice. P + F group showed improved insulin resistance and similar body weight gain, as compared with control group. The mRNA expression of genes related to fatty acid oxidation was markedly up-regulated in the liver of P + F group. Pioglitazone administration markedly decreased the phosphorylation levels of AMPK, as compared with all other groups. Besides, even though plasma adiponectin increased in PIO, FT-5, P + F group, adipoR2 gene expression significantly decreased in the liver of PIO group.
FT-5 decreased plasma TG and alleviated aggravating hepatic steatosis induced by pioglitazone in KKAy mice. FT-5's mechanism might be associated with its ability to activate the AdipoR2/AMPK pathway.
评估五种草药提取物混合物（FT - 5）对胰岛素抵抗、糖脂代谢、肝脂肪变性的影响，并研究FT - 5与吡格列酮联合使用是否能在糖尿病A y基因（KKAy）小鼠中对糖尿病治疗产生显著效果，同时可能将吡格列酮的不良副作用降至最低。
将7周龄的KKAy小鼠随机分为五组：对照组（CON）、FT - 5（2.0 g/kg）组、吡格列酮（20 mg/kg）（PIO）组、吡格列酮（20 mg/kg）+ FT - 5（2.0 g/kg）（P + F）组。将年龄匹配的C57BL/6J小鼠作为对照组。连续灌胃给药7周后，通过评估空腹血糖（FBG）、口服葡萄糖耐量试验（OGTT）、空腹血清胰岛素（FINS）、胰岛素耐量试验（ITT）、稳态模型评估胰岛素抵抗指数（HOMA - IR）、血浆和肝脏中的总胆固醇（TC）、总甘油三酯（TG）和游离脂肪酸（FFA）来评估KKAy小鼠的糖代谢、胰岛素敏感性和脂代谢。通过酶联免疫吸附测定法测量血浆和肝脏中的脂联素。通过实时聚合酶链反应检测白色脂肪组织（WAT）和肝脏中与脂肪生成和脂肪分解相关的基因。通过蛋白质印迹法检测KKAy小鼠肝脏中与脂质代谢相关的蛋白质表达。
PIO治疗显著改善了胰岛素抵抗。然而，它也显示出明显的副作用。FT - 5组血清葡萄糖没有显著降低。然而，它降低了空腹血浆TG水平并改善了KKAy小鼠的肝脂肪变性。与对照组相比，P + F组显示出改善的胰岛素抵抗和相似的体重增加。P + F组肝脏中与脂肪酸氧化相关基因的mRNA表达明显上调。与所有其他组相比，吡格列酮给药显著降低了AMPK的磷酸化水平。此外，尽管PIO、FT - 5、P + F组血浆脂联素增加，但PIO组肝脏中adipoR2基因表达显著降低。
FT - 5降低了KKAy小鼠的血浆TG，并减轻了吡格列酮诱导的肝脂肪变性加重。FT - 5的作用机制可能与其激活AdipoR2/AMPK途径的能力有关。
