Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine; Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China; Institute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center; Guangdong TCM Key Laboratory for Metabolic Diseases, 280 Wai Huan Dong Road, Guangzhou, 510006, China.
BMC Complement Med Ther. 2023 Jun 19;23(1):202. doi: 10.1186/s12906-023-04009-5.
Tianhuang formula (THF) is a Chinese medicine prescription that is patented and clinically approved, and has been shown to improve energy metabolism, but the underlying mechanism remains poorly understood. The purpose of this study is to clarify the potential mechanisms of THF in the treatment of type 2 diabetes mellitus (T2DM).
A murine model of T2DM was induced by high-fat diet (HFD) feeding combined with low-dose streptozocin (STZ) injections, and the diabetic mice were treated with THF by gavaging for consecutive 10 weeks. Fasting blood glucose (FBG), serum insulin, blood lipid, mitochondrial Ca (mCa) levels and mitochondrial membrane potential (MMP), as well as ATP production were analyzed. The target genes and proteins expression of visceral adipose tissue (Vat) was tested by RT-PCR and western blot, respectively. The underlying mechanism of the regulating energy metabolism effect of THF was further explored in the insulin resistance model of 3T3-L1 adipocytes cultured with dexamethasone (DXM).
THF restored impaired glucose tolerance and insulin resistance in diabetic mice. Serum levels of lipids were significantly decreased, as well as fasting blood glucose and insulin in THF-treated mice. THF regulated Ca uptake, increased MMP and ATP content in VAT. THF increased the mRNA and protein expression of AMPK, phosphorylated AMPK (p-AMPK), MICU1, sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). THF could increase the Ca level of 3T3-L1 adipocytes and regulate mitochondrial function. The protein expression of AMPK, p-AMPK, Ca uniporter (MCU) and MICU1 decreased upon adding AMPK inhibitor compound C to 3T3-L1 adipocytes and the protein expression of MCU and MICU1 decreased upon adding the MCU inhibitor ruthenium red.
These results demonstrated that THF ameliorated glucose and lipid metabolism disorders in T2DM mice through the improvement of AMPK/MICU1 pathway-dependent mitochondrial function in adipose tissue.
天花粉配方（THF）是一种中药方剂，已获得专利并在临床上得到认可，可改善能量代谢，但作用机制尚不清楚。本研究旨在阐明 THF 治疗 2 型糖尿病（T2DM）的潜在机制。
通过高脂肪饮食（HFD）喂养联合小剂量链脲佐菌素（STZ）注射诱导 T2DM 小鼠模型，并用 THF 通过灌胃连续治疗 10 周。分析空腹血糖（FBG）、血清胰岛素、血脂、线粒体钙（mCa）水平和线粒体膜电位（MMP）以及 ATP 产生。通过 RT-PCR 和 Western blot 分别检测内脏脂肪组织（Vat）的靶基因和蛋白表达。进一步在培养有地塞米松（DXM）的 3T3-L1 脂肪细胞胰岛素抵抗模型中探讨 THF 调节能量代谢作用的潜在机制。
THF 恢复了糖尿病小鼠受损的葡萄糖耐量和胰岛素抵抗。THF 治疗组小鼠血清脂质水平显著降低，空腹血糖和胰岛素水平也降低。THF 调节 VAT 中的 Ca 摄取，增加 MMP 和 ATP 含量。THF 增加了 AMPK、磷酸化 AMPK（p-AMPK）、MICU1、SIRT1 和过氧化物酶体增殖物激活受体-γ共激活物-1α（PGC-1α）的 mRNA 和蛋白表达。THF 可增加 3T3-L1 脂肪细胞的 Ca 水平并调节线粒体功能。在 3T3-L1 脂肪细胞中加入 AMPK 抑制剂化合物 C 后，AMPK、p-AMPK、钙单向转运蛋白（MCU）和 MICU1 的蛋白表达降低，加入 MCU 抑制剂钌红后，MCU 和 MICU1 的蛋白表达降低。
这些结果表明，THF 通过改善脂肪组织中 AMPK/MICU1 通路依赖性线粒体功能，改善 T2DM 小鼠的葡萄糖和脂质代谢紊乱。
