PMID- 34025574
OWN - NLM
STAT- MEDLINE
DCOM- 20211220
LR  - 20211220
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 12
DP  - 2021
TI  - Berberine Slows the Progression of Prediabetes to Diabetes in Zucker Diabetic 
      Fatty Rats by Enhancing Intestinal Secretion of Glucagon-Like Peptide-2 and 
      Improving the Gut Microbiota.
PG  - 609134
LID - 10.3389/fendo.2021.609134 [doi]
LID - 609134
AB  - BACKGROUND: Berberine is a plant alkaloid that has multiple beneficial effects 
      against intestine inflammation. In our previous study, we have found that 
      berberine also possesses an antidiabetic effect. However, whether berberine is 
      useful in the prevention of type 2 diabetes mellitus (T2DM) through its effect on 
      intestine endocrine function and gut microbiota is unclear. AIM: To investigate 
      the effects of berberine in the prevention of T2DM, as well as its effects on 
      intestine GLP-2 secretion and gut microbiota in ZDF rats. METHODS: Twenty Zucker 
      Diabetic Fatty (ZDF) rats were fed a high-energy diet until they exhibited 
      impaired glucose tolerance (IGT). The rats were then divided into two groups to 
      receive berberine (100 mg/kg/d; berberine group) or vehicle (IGT group) by gavage 
      for 3 weeks. Five Zucker Lean (ZL) rats were used as controls. Fasting blood 
      glucose (FBG) was measured, an oral glucose tolerance test was performed, and the 
      Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated. 
      Intestinal expression of TLR-4, NF-kappaB, TNF-alpha, mucin, zona occludens-1 (ZO-1) and 
      occludin were assessed (immunohistochemistry). Plasma levels and 
      glutamine-induced intestinal secretion of glucagon-like peptide-1 (GLP-1) and 
      GLP-2 were measured (enzyme-linked immunosorbent assay). The plasma 
      lipopolysaccharide (LPS) level was measured. Fecal DNA extraction, 
      pyrosequencing, and bioinformatics analysis were performed. RESULTS: After 3 
      weeks of intervention, diabetes developed in all rats in the IGT group, but only 
      30% of rats in the berberine group. Treatment with berberine was associated with 
      reductions in food intake, FBG level, insulin resistance, and plasma LPS level, 
      as well as increases in fasting plasma GLP-2 level and glutamine-induced 
      intestinal GLP-2 secretion. Berberine could increase the goblet cell number and 
      villi length, and also reverse the suppressed expressions of mucin, occludin, 
      ZO-1 and the upregulated expressions of TLR-4, NF-kappaB and TNF-alpha induced in IGT 
      rats (P<0.05). Berberine also improved the structure of the gut microbiota and 
      restored species diversity. CONCLUSION: Berberine may slow the progression of 
      prediabetes to T2DM in ZDF rats by improving GLP-2 secretion, intestinal 
      permeability, and the structure of the gut microbiota.
CI  - Copyright (c) 2021 Wang, Liu, Zheng, Yang, Ren, Kong, Wang, Wang, Jiang, Yang and 
      Shan.
FAU - Wang, Ying
AU  - Wang Y
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Liu, Haiyi
AU  - Liu H
AD  - Department of Pediatrics, Cangzhou People's Hospital, Cangzhou, China.
FAU - Zheng, Miaoyan
AU  - Zheng M
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Yang, Yanhui
AU  - Yang Y
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Ren, Huizhu
AU  - Ren H
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Kong, Yan
AU  - Kong Y
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Wang, Shanshan
AU  - Wang S
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Wang, Jingyu
AU  - Wang J
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Jiang, Yingying
AU  - Jiang Y
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Yang, Juhong
AU  - Yang J
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
FAU - Shan, Chunyan
AU  - Shan C
AD  - National Health Council (NHC) Key Laboratory of Hormones and Development, Tianjin 
      Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin 
      Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210507
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
RN  - 0 (Glucagon-Like Peptide 2)
RN  - 0I8Y3P32UF (Berberine)
SB  - IM
MH  - Animals
MH  - Berberine/*pharmacology/therapeutic use
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Experimental/metabolism/microbiology/prevention & control
MH  - Diabetes Mellitus, Type 2/metabolism/microbiology/prevention & control
MH  - Disease Progression
MH  - Gastrointestinal Microbiome/*drug effects
MH  - Glucagon-Like Peptide 2/*metabolism
MH  - Intestinal Mucosa/*drug effects/metabolism/microbiology/pathology
MH  - Intestinal Secretions/drug effects/metabolism
MH  - Male
MH  - Obesity/complications/metabolism/microbiology/pathology
MH  - *Prediabetic State/drug therapy/metabolism/microbiology/pathology
MH  - Rats
MH  - Rats, Zucker
PMC - PMC8138858
OTO - NOTNLM
OT  - berberine
OT  - glucagon-like peptide-2
OT  - intestinal microbiota
OT  - intestinal permeability
OT  - type 2 diabetes mellitus
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- 2021/05/25 06:00
MHDA- 2021/12/21 06:00
PMCR- 2021/01/01
CRDT- 2021/05/24 08:04
PHST- 2020/09/22 00:00 [received]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/05/24 08:04 [entrez]
PHST- 2021/05/25 06:00 [pubmed]
PHST- 2021/12/21 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2021.609134 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2021 May 7;12:609134. doi: 
      10.3389/fendo.2021.609134. eCollection 2021.