The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis
| Autor: | Lixin Sun, Lu Wang, Hong-fei Huang, Luyong Zhang, Dengqiu Xu, Tao Wang, Li Zhijian, Chunjie Li, Zhenzhou Jiang, Sisi Fan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male AMPK Mitochondrial DNA Glucose uptake Iridoid Glucosides Administration Oral catalpol Mitochondrion AMP-Activated Protein Kinases Article 03 medical and health sciences chemistry.chemical_compound Mice Structure-Activity Relationship 0302 clinical medicine Animals Hypoglycemic Agents Pharmacology (medical) NRF1 skeletal muscle Muscle Skeletal Cells Cultured Pharmacology Dose-Response Relationship Drug Chemistry General Medicine TFAM Glucose Tolerance Test biogenesis Catalpol Cell biology Mitochondria Mice Inbred C57BL 030104 developmental biology Mitochondrial biogenesis 030220 oncology & carcinogenesis type 2 diabetes |
| Zdroj: | Acta Pharmacologica Sinica |
| ISSN: | 1745-7254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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