PMID- 38351702
OWN - NLM
STAT- MEDLINE
DCOM- 20240312
LR  - 20240312
IS  - 1793-6853 (Electronic)
IS  - 0192-415X (Linking)
VI  - 52
IP  - 1
DP  - 2024
TI  - Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress 
      and Mitochondrial Dysfunction.
PG  - 253-274
LID - 10.1142/S0192415X24500113 [doi]
AB  - Berberine (BBR) is a principal component of Rhizoma coptidis known for its 
      therapeutic potential in treating diseases such as type 2 diabetes mellitus 
      (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that 
      its metabolites play a pivotal role in its biological activities. While BBR is 
      recognized to promote GLP-1 production in intestinal L cells, the cytoprotective 
      effects of its metabolites on these cells are yet to be explored. The present 
      study investigates the effects of BBR metabolites on GLP-1 secretion and the 
      underlying mechanisms. Our results revealed that, out of six BBR metabolites, 
      berberrubine (BBB) and palmatine (PMT) significantly increased the production and 
      glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT 
      could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in 
      standard mice. Moreover, a single dose of PMT could markedly increase plasma 
      GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat 
      diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and 
      PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. 
      Furthermore, they could effectively reverse inflammation-induced inhibition of 
      the Akt signaling pathway. In general, these insights suggest that the beneficial 
      effects of orally administered BBR on GLP-1 secretion are largely attributed to 
      the pharmacological activity of BBB and PMT by their above cytoprotective effects 
      on L cells, which provide important ideas for stimulating GLP-1 secretion and the 
      treatment of T2DM.
FAU - Yang, Wei-Li
AU  - Yang WL
AUID- ORCID: 0000-0003-3646-7772
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
FAU - Zhang, Chen-Yang
AU  - Zhang CY
AUID- ORCID: 0000-0002-8582-7538
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
FAU - Ji, Wen-Yi
AU  - Ji WY
AUID- ORCID: 0009-0004-0873-0339
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
FAU - Zhao, Li-Li
AU  - Zhao LL
AUID- ORCID: 0000-0003-2709-8733
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
FAU - Yang, Fang-Yuan
AU  - Yang FY
AUID- ORCID: 0009-0002-2570-0268
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
FAU - Zhang, Lin
AU  - Zhang L
AUID- ORCID: 0000-0002-7137-5155
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
FAU - Cao, Xi
AU  - Cao X
AUID- ORCID: 0000-0001-5447-6766
AD  - Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, 
      Department of Endocrinology, Beijing Tongren Hospital, Capital Medical 
      University, Beijing 100730, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20240208
PL  - Singapore
TA  - Am J Chin Med
JT  - The American journal of Chinese medicine
JID - 7901431
RN  - 0I8Y3P32UF (Berberine)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Berberine/pharmacology/therapeutic use
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Glucagon-Like Peptide 1/metabolism/pharmacology/therapeutic use
MH  - Glucose
MH  - Obesity/metabolism
MH  - Oxidative Stress
MH  - *Mitochondrial Diseases/drug therapy
OTO - NOTNLM
OT  - Berberrubine
OT  - GLP-1
OT  - Mitochondrial Dysfunction
OT  - Oxidative Stress
OT  - Palmatine
EDAT- 2024/02/14 06:43
MHDA- 2024/03/12 06:42
CRDT- 2024/02/14 02:33
PHST- 2024/03/12 06:42 [medline]
PHST- 2024/02/14 06:43 [pubmed]
PHST- 2024/02/14 02:33 [entrez]
AID - 10.1142/S0192415X24500113 [doi]
PST - ppublish
SO  - Am J Chin Med. 2024;52(1):253-274. doi: 10.1142/S0192415X24500113. Epub 2024 Feb 
      8.