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  3. Real-time monitoring of glucose metabolism and effects of metformin on HepG2 cells using 13C in-cell NMR spectroscopy

Real-time monitoring of glucose metabolism and effects of metformin on HepG2 cells using 13C in-cell NMR spectroscopy

  • Biochem Biophys Res Commun. 2023 Dec 19:694:149383. doi: 10.1016/j.bbrc.2023.149383.
Muzhou Teng 1,  Zhijia Li 2,  Yanmei Gu 1,  Yitao Fan 1,  Daijun Wang 1,  Meiyu Liu 3,  Yumin Li 4,  Gang Wei 5,  Yanjie Huang 6
Affiliations

Affiliations

  • 1 Key Laboratory of the Digestive System Tumors of Gansu Province, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, 730000, Gansu, China.
  • 2 Dermatology Hospital, Southern Medical University, Guangzhou, 510091, China.
  • 3 Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China.
  • 4 Key Laboratory of the Digestive System Tumors of Gansu Province, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, 730000, Gansu, China. Electronic address: liym@lzu.edu.cn.
  • 5 Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Diabetes Institute, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. Electronic address: gangwei_2013@163.com.
  • 6 Henan University of Chinese Medicine, Zhengzhou, Henan, 450046, China; Engineering Technology Research Center for Comprehensive Development and Utilization of Authentic Medicinal Materials in Henan Province, Zhengzhou, Henan, 450046, China. Electronic address: hyj0106@foxmail.com.
PMID: 38150918 DOI: 10.1016/j.bbrc.2023.149383
Abstract

Metformin is currently a strong candidate antitumor agent for multiple cancers, and has the potential to inhibit Cancer cell viability, growth, and proliferation. Metabolic reprogramming is a critical feature of Cancer cells. However, the effects of metformin which targets glucose metabolism on HepG2 Cancer cells remain unclear. In this study, to explore the effects of metformin on glucose metabolism in HepG2 cells, we conducted real-time metabolomic monitoring of live HepG2 cells treated with metformin using 13C in-cell NMR spectroscopy. Metabolic tracing with U-13C6-glucose revealed that metformin significantly increased the production of 13C-G3P and 13C-glycerol, which were reported to attenuate liver Cancer development, but decreased the production of potential oncogenesis-supportive metabolites, including 13C-lactate, 13C-alanine, 13C-glycine, and 13C-glutamate. Moreover, the expression levels of Enzymes associated with the measured metabolites were carried out. The results showed that the levels of ALT1, MCT4, GPD2 and MPC1 were greatly reduced, which were consistent with the changes of measured metabolites in 13C in-cell NMR spectroscopy. Overall, our approach directly provides fundamental insights into the effects of metformin on glucose metabolism in live HepG2 cells, and highlights the potential mechanism of metformin, including the increase in production of G3P and glycerol derived from glucose, as well as the inhibition of glucose incorporation into lactate, alanine, glutamate, and glycine.

Keywords

Glutamate excretion; Glycerol metabolism; Glycine metabolism.

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