Evidence connecting old,new and neglected glucose‐lowering drugs to bile acid‐induced GLP‐1 secretion: A review |
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| Authors: | Martin L. Kårhus BSc Andreas Brønden MD David P. Sonne MD PhD Tina Vilsbøll MD DMSc Fillip K. Knop MD PhD |
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| Affiliation: | 1. Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark;2. Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark;3. Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;4. Steno Diabetes Center, Copenhagen, University of Copenhagen, Gentofte, Denmark;5. Faculty of Health and Medical Sciences, The Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark |
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| Abstract: | Bile acids are amphipathic water‐soluble steroid‐based molecules best known for their important lipid‐solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose‐lowering potential. Among a variety of gluco‐metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut‐derived incretin hormone glucagon‐like peptide‐1 (GLP‐1), possibly via the transmembrane receptor Takeda G‐protein‐coupled receptor 5 and the nuclear farnesoid X receptor, in intestinal L cells. The present article critically reviews current evidence connecting established glucose‐lowering drugs to bile acid‐induced GLP‐1 secretion, and discusses whether bile acid‐induced GLP‐1 secretion may constitute a new basis for understanding how metformin, inhibitors of the apical sodium‐dependent bile acids transporter, and bile acid sequestrants – old, new and neglected glucose‐lowering drugs – improve glucose metabolism. |
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| Keywords: | antidiabetic drug ASBT inhibitors, bile acid, bile acid sequestrants, drug mechanism
GLP‐1 incretin therapy metformin type 2 diabetes |
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