Department of Endocrinology, Affiliated Renhe Hospital of China Three Gorges University, The Second Clinical Medical College of China Three Gorges University, Yichang, China.
Yichang Hospital of Traditional Chinese Medicine, Clinical Medical College of Traditional Chinese Medicine, China Three Gorges University, Yichang, China.
J Int Med Res. 2020 May;48(5):300060519885569. doi: 10.1177/0300060519885569.
To evaluate the effect of sitagliptin on skeletal muscle expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), irisin, and phosphoadenylated adenylate activated protein kinase (p-AMPK) in a rat model of type 2 diabetes mellitus (T2DM).
A high-fat diet/streptozotocin T2DM rat model was established. Rats were divided into T2DM, low-dose sitagliptin (ST1), high-dose sitagliptin (ST2), and normal control groups (NC). PGC-1α, irisin, and p-AMPK protein levels in skeletal muscle were measured by western blot, and PCG-1α and Fndc5 mRNA levels were assessed by reverse transcription-polymerase chain reaction.
Fasting plasma glucose (FPG), fasting insulin (FIns), homeostatic model assessment-insulin resistance (HOMA-IR), and tumor necrosis factor-α (TNF-α) were significantly up-regulated in the T2DM compared with the other groups, and FPG, FIns, total cholesterol, triglycerides, TNF-α, and HOMA-IR were significantly down-regulated in the ST2 compared with the ST1 group. PGC-1α, irisin, and p-AMPK expression levels decreased successively in the ST2, ST1, and DM groups compared with the NC, and were all significantly up-regulated in the ST2 compared with the ST1 group.
Down-regulation of PGC-1α and irisin in skeletal muscle may be involved in T2DM. Sitagliptin can dose-dependently up-regulate PCG-1α and irisin, potentially improving insulin resistance and glycolipid metabolism and inhibiting inflammation.
评估西他列汀对 2 型糖尿病（T2DM）大鼠模型骨骼肌组织过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）、鸢尾素和磷酸腺苷激活的蛋白激酶（p-AMPK）表达的影响。
建立高脂肪饮食/链脲佐菌素 T2DM 大鼠模型。将大鼠分为 T2DM 组、低剂量西他列汀（ST1）组、高剂量西他列汀（ST2）组和正常对照组（NC）。采用 Western blot 法检测骨骼肌组织中 PGC-1α、鸢尾素和 p-AMPK 蛋白水平，逆转录-聚合酶链反应（RT-PCR）法检测 PCG-1α 和 Fndc5mRNA 水平。
与其他组相比，T2DM 组大鼠空腹血糖（FPG）、空腹胰岛素（FIns）、稳态模型评估-胰岛素抵抗（HOMA-IR）和肿瘤坏死因子-α（TNF-α）水平显著升高，与 ST1 组相比，ST2 组 FPG、FIns、总胆固醇、甘油三酯、TNF-α和 HOMA-IR 水平显著降低。与 NC 组相比，ST2、ST1 和 DM 组大鼠骨骼肌组织中 PGC-1α、鸢尾素和 p-AMPK 表达水平依次降低，与 ST1 组相比，ST2 组大鼠上述蛋白表达水平均显著升高。
骨骼肌组织中 PGC-1α 和鸢尾素的下调可能与 T2DM 有关。西他列汀可剂量依赖性地上调 PCG-1α 和鸢尾素，可能改善胰岛素抵抗和糖脂代谢，抑制炎症反应。
