PMID- 31468642
OWN - NLM
STAT- MEDLINE
DCOM- 20210402
LR  - 20210402
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 22
IP  - 2
DP  - 2020 Feb
TI  - Mechanism of glucose-lowering by metformin in type 2 diabetes: Role of bile 
      acids.
PG  - 141-148
LID - 10.1111/dom.13869 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is an increasingly prevalent chronic condition, 
      characterized by abnormally elevated blood glucose concentrations and, as a 
      consequence, increased risk of micro- and macrovascular complications. Metformin 
      is usually the first-line glucose-lowering medication in T2DM; however, despite 
      being used for more than 60 years, the mechanism underlying the glucose-lowering 
      action of metformin remains incompletely understood. Although metformin reduces 
      hepatic glucose production, there is persuasive evidence that the 
      gastrointestinal tract is crucial in mediating this effect, particularly via 
      secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). It is now well 
      recognized that bile acids, in addition to their established function in fat 
      digestion and absorption, are important regulators of glucose metabolism. 
      Exposure of the small and large intestine to bile acids induces GLP-1 secretion, 
      modulates the composition of the gut microbiota, and reduces postprandial blood 
      glucose excursions in humans with and without T2DM. Metformin reduces intestinal 
      bile acid resorption substantially, such that intraluminal bile acids may, at 
      least in part, account for its glucose-lowering effect. The present review 
      focuses on the conceptual shift in our understanding as to how metformin lowers 
      blood glucose in T2DM, with a particular emphasis on the role of intestinal bile 
      acids.
CI  - (c) 2019 John Wiley & Sons Ltd.
FAU - Sansome, Daniel J
AU  - Sansome DJ
AUID- ORCID: 0000-0002-5618-9602
AD  - Adelaide Medical School and Centre of Research Excellence in Translating 
      Nutritional Science to Good Health, University of Adelaide, Adelaide, South 
      Australia, Australia.
FAU - Xie, Cong
AU  - Xie C
AD  - Adelaide Medical School and Centre of Research Excellence in Translating 
      Nutritional Science to Good Health, University of Adelaide, Adelaide, South 
      Australia, Australia.
FAU - Veedfald, Simon
AU  - Veedfald S
AD  - Adelaide Medical School and Centre of Research Excellence in Translating 
      Nutritional Science to Good Health, University of Adelaide, Adelaide, South 
      Australia, Australia.
AD  - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Horowitz, Michael
AU  - Horowitz M
AD  - Adelaide Medical School and Centre of Research Excellence in Translating 
      Nutritional Science to Good Health, University of Adelaide, Adelaide, South 
      Australia, Australia.
FAU - Rayner, Christopher K
AU  - Rayner CK
AUID- ORCID: 0000-0002-5527-256X
AD  - Adelaide Medical School and Centre of Research Excellence in Translating 
      Nutritional Science to Good Health, University of Adelaide, Adelaide, South 
      Australia, Australia.
FAU - Wu, Tongzhi
AU  - Wu T
AUID- ORCID: 0000-0003-1656-9210
AD  - Adelaide Medical School and Centre of Research Excellence in Translating 
      Nutritional Science to Good Health, University of Adelaide, Adelaide, South 
      Australia, Australia.
AD  - Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, School of 
      Medicine, Southeast University, Nanjing, China.
LA  - eng
GR  - Y19G-WUTO/Diabetes Australia Research Trust/International
GR  - APP1147333/Australian National Health and Medical Research Council 
      (NHMRC)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20191007
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Bile Acids and Salts)
RN  - 0 (Blood Glucose)
RN  - 9100L32L2N (Metformin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Bile Acids and Salts/pharmacology/*physiology
MH  - Blood Glucose/*drug effects/metabolism
MH  - Carbohydrate Metabolism/drug effects
MH  - Diabetes Mellitus, Type 2/*blood/*drug therapy
MH  - Glucose/metabolism
MH  - Humans
MH  - Intestinal Mucosa/drug effects/metabolism
MH  - Intestines/drug effects
MH  - Metabolic Networks and Pathways/drug effects
MH  - Metformin/*pharmacology/therapeutic use
OTO - NOTNLM
OT  - bile acids
OT  - gastrointestinal function
OT  - glucagon-like peptide-1
OT  - metformin
OT  - postprandial glycaemia
OT  - type 2 diabetes
EDAT- 2019/08/31 06:00
MHDA- 2021/04/07 06:00
CRDT- 2019/08/31 06:00
PHST- 2019/07/11 00:00 [received]
PHST- 2019/08/07 00:00 [revised]
PHST- 2019/08/28 00:00 [accepted]
PHST- 2019/08/31 06:00 [pubmed]
PHST- 2021/04/07 06:00 [medline]
PHST- 2019/08/31 06:00 [entrez]
AID - 10.1111/dom.13869 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2020 Feb;22(2):141-148. doi: 10.1111/dom.13869. Epub 2019 
      Oct 7.