Laboratorio de Farmacología, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, México.
Departamento de Farmacología y Toxicología, Hospital Infantil de México Federico Gómez, Ciudad de México, México.
Can J Physiol Pharmacol. 2021 Sep;99(9):935-942. doi: 10.1139/cjpp-2021-0027. Epub 2021 Feb 17.
α-Amyrin, a natural pentacyclic triterpene, has an antihyperglycemic effect in mice and dual PPARδ/γ action in 3T3-L1 adipocytes, and potential in the control of type 2 diabetes (T2D). About 80% of glucose uptake occurs in skeletal muscle cells, playing a significant role in insulin resistance (IR) and T2D. Peroxisome-proliferator activated receptors (PPARs), in particular PPARδ and PPARγ, are involved in the regulation of lipids and carbohydrates and, along with adenosine-monophosphate (AMP) - activated protein kinase (AMPK) and protein kinase B (Akt), are implicated in translocation of glucose transporter 4 (GLUT4); however, it is still unknown whether α-amyrin can affect these pathways in skeletal muscle cells. Our objective was to determine the action of α-amyrin in PPARδ, PPARγ, AMPK, and Akt in C2C12 myoblasts. The expression of PPARδ, PPARγ, fatty acid transporter protein (FATP), and GLUT4 was quantified using reverse transcription quantitative PCR and Western blot. α-Amyrin increased these markers along with phospho-AMPK (p-AMPK) but not p-Akt. Molecular docking showed that α-amyrin acts as an AMPK-allosteric activator, and may be related to GLUT4 translocation, as evidenced by confocal microscopy. These data support that α-amyrin could have an insulin-mimetic action in C2C12 myoblasts and should be considered as a bioactive molecule for new multitarget drugs with utility in T2D and other metabolic diseases.
α-香树精，一种天然的五环三萜，在小鼠中具有降血糖作用，在 3T3-L1 脂肪细胞中有双重过氧化物酶体增殖物激活受体 δ/γ作用，有望用于控制 2 型糖尿病（T2D）。大约 80%的葡萄糖摄取发生在骨骼肌细胞中，在胰岛素抵抗（IR）和 T2D 中起着重要作用。过氧化物酶体增殖物激活受体（PPARs），特别是 PPARδ 和 PPARγ，参与脂质和碳水化合物的调节，与单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）和蛋白激酶 B（Akt）一起，参与葡萄糖转运蛋白 4（GLUT4）的易位；然而，目前尚不清楚α-香树精是否可以影响骨骼肌细胞中的这些途径。我们的目的是确定α-香树精在 C2C12 成肌细胞中对 PPARδ、PPARγ、AMPK 和 Akt 的作用。使用逆转录定量 PCR 和 Western blot 定量检测 PPARδ、PPARγ、脂肪酸转运蛋白（FATP）和 GLUT4 的表达。α-香树精增加了这些标志物以及磷酸化 AMPK（p-AMPK）但不增加磷酸化 Akt。分子对接表明，α-香树精作为 AMPK 变构激活剂，可能与 GLUT4 易位有关，共聚焦显微镜证明了这一点。这些数据支持α-香树精在 C2C12 成肌细胞中可能具有胰岛素模拟作用，并且应该被认为是一种具有多靶点药物的生物活性分子，可用于 T2D 和其他代谢性疾病。
