PMID- 34122092
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210615
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Kun-Dan Decoction Ameliorates Insulin Resistance by Activating AMPK/mTOR-Mediated 
      Autophagy in High-Fat Diet-Fed Rats.
PG  - 670151
LID - 10.3389/fphar.2021.670151 [doi]
LID - 670151
AB  - Background: Metabolic syndrome is characterized by central obesity, hyperglycemia 
      and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic 
      syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been 
      applied to treat patients with metabolic syndrome for over ten years. It is 
      increasingly recognized that autophagy deficiency is the key cause of metabolic 
      syndrome. Therefore, we aimed to explore whether KD can activate autophagy to 
      improve metabolic syndrome. Methods: Network pharmacology was used to explore the 
      underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat 
      diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral 
      glucose tolerance test and insulin tolerance test, obesity and histological 
      examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol 
      (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model 
      assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat 
      diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 
      5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian 
      target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, 
      Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 
      3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator 
      rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 
      were utilized to verify the role of autophagy in the treatment of metabolic 
      syndrome by KD in oleic acid-induced LO2 cells. Results: Results from network 
      pharmacology indicated that targeted insulin resistance might be the critical 
      mechanism of KD in the treatment of metabolic syndrome. We found that KD 
      significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C 
      levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD 
      enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. 
      Western blot showed that KD could enhance autophagy to increase the insulin 
      sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. 
      Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse 
      the protective effect of KD on LO2 cells. However, rapamycin could cooperate with 
      KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells. 
      Conclusion: The induction of autophagy may be the major mechanism for KD to 
      improve insulin resistance and metabolic syndrome.
CI  - Copyright (c) 2021 Su, Zeng, Feng, Tang, Sun, Wang, Li, Zheng and Zhu.
FAU - Su, Zuqing
AU  - Su Z
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Zeng, Kexue
AU  - Zeng K
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Feng, Bing
AU  - Feng B
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Tang, Lipeng
AU  - Tang L
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Sun, Chaoyue
AU  - Sun C
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Wang, Xieqi
AU  - Wang X
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Li, Caiyun
AU  - Li C
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Zheng, Guangjuan
AU  - Zheng G
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
FAU - Zhu, Ying
AU  - Zhu Y
AD  - Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of 
      Guangzhou University of Chinese Medicine, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20210528
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8193673
OTO - NOTNLM
OT  - AMPK/mTOR-mediated autophagy
OT  - Kun-Dan decoction
OT  - insulin resistance
OT  - metabolic syndrome
OT  - network pharmacology
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/15 06:00
MHDA- 2021/06/15 06:01
PMCR- 2021/05/28
CRDT- 2021/06/14 09:35
PHST- 2021/02/20 00:00 [received]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/06/14 09:35 [entrez]
PHST- 2021/06/15 06:00 [pubmed]
PHST- 2021/06/15 06:01 [medline]
PHST- 2021/05/28 00:00 [pmc-release]
AID - 670151 [pii]
AID - 10.3389/fphar.2021.670151 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 May 28;12:670151. doi: 10.3389/fphar.2021.670151. 
      eCollection 2021.