Bile Acids Acutely Stimulate Insulin Secretion of Mouse β-Cells via Farnesoid X Receptor Activation and KATP Channel Inhibition

  1. Gisela Drews1
  1. 1Department of Pharmacology, Institute of Pharmacy, University of Tübingen, Tübingen, Germany
  2. 2Department of Cell Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California
  3. 3Institute of Physiology and Pathophysiology, University of Marburg, Marburg, Germany
  4. 4National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  1. Corresponding author: Martina Düfer, martina.duefer{at}
  1. M.D. and K.H. contributed equally to this study.


Type 2 diabetes mellitus is associated with alterations in bile acid (BA) signaling. The aim of our study was to test whether pancreatic β-cells contribute to BA-dependent regulation of glucose homeostasis. Experiments were performed with islets from wild-type, farnesoid X receptor (FXR) knockout (KO), and β-cell ATP-dependent K+ (KATP) channel gene SUR1 (ABCC8) KO mice, respectively. Sodium taurochenodeoxycholate (TCDC) increased glucose-induced insulin secretion. This effect was mimicked by the FXR agonist GW4064 and suppressed by the FXR antagonist guggulsterone. TCDC and GW4064 stimulated the electrical activity of β-cells and enhanced cytosolic Ca2+ concentration ([Ca2+]c). These effects were blunted by guggulsterone. Sodium ursodeoxycholate, which has a much lower affinity to FXR than TCDC, had no effect on [Ca2+]c and insulin secretion. FXR activation by TCDC is suggested to inhibit KATP current. The decline in KATP channel activity by TCDC was only observed in β-cells with intact metabolism and was reversed by guggulsterone. TCDC did not alter insulin secretion in islets of SUR1-KO or FXR-KO mice. TCDC did not change islet cell apoptosis. This is the first study showing an acute action of BA on β-cell function. The effect is mediated by FXR by nongenomic elements, suggesting a novel link between FXR activation and KATP channel inhibition.


  • Received June 15, 2011.
  • Accepted February 7, 2012.

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