Article

The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis

Deng-qiu Xu1, Chun-jie Li1, Zhen-zhou Jiang1,2, Lu Wang1, Hong-fei Huang3, Zhi-jian Li1,4, Li-xin Sun1,2, Si-si Fan1, Lu-yong Zhang1,2,5, Tao Wang1,6
1 Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
2 Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009, China
3 School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
4 Department of Toxicology Laboratory, Xinjiang Institute of Traditional Uyghur Medicine, Xinjiang Laboratory of Uyghur Medical Prescription, Urumqi 830049, China
5 Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China
6 Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China
Correspondence to: Lu-yong Zhang: lyzhang@cpu.edu.cn, Tao Wang: wangtao1331@cpu.edu.cn,
DOI: 10.1038/s41401-019-0345-2
Received: 25 August 2019
Accepted: 2 December 2019
Advance online: 14 January 2020

Abstract

Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro. After oral administration of catalpol (200 mg·kg−1·d−1) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. Catalpol increased mitochondrial biogenesis, evidenced by significant elevations in the number of mitochondria, mitochondrial DNA levels, and the expression of three genes associated with mitochondrial biogenesis: peroxisome proliferator-activated receptor gammaco-activator 1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1). In C2C12 myotubes, catalpol significantly increased glucose uptake and ATP production. These effects depended on activation of AMP-activated protein kinase (AMPK)-mediated mitochondrial biogenesis. Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. These findings may guide the development of a new therapeutic approach for type 2 diabetes.
Keywords: catalpol; AMPK; mitochondria; biogenesis; type 2 diabetes; skeletal muscle

Article Options

Download Citation

Cited times in Scopus

Share