Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell.
- Menegaz D Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
- Hagan DW J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
- Almaça J Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
- Cianciaruso C Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Rodriguez-Diaz R Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
- Molina J Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
- Dolan RM J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
- Becker MW J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
- Schwalie PC Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Nano R Pancreatic Islet Processing Facility, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Lebreton F Cell Isolation and Transplantation Center, Faculty of Medicine, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
- Kang C Center for Cardiovascular Research and Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
- Sah R Center for Cardiovascular Research and Division of Cardiology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
- Gaisano HY Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Berggren PO Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
- Baekkeskov S Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. sbaekkeskov@ucsf.edu.
- Caicedo A Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. acaicedo@med.miami.edu.
- Phelps EA J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA. ephelps@bme.ufl.edu.
- 2020-05-21
Published in:
- Nature metabolism. - 2019
English
Pancreatic beta cells synthesize and secrete the neurotransmitter γ-aminobutyric acid (GABA) as a paracrine and autocrine signal to help regulate hormone secretion and islet homeostasis. Islet GABA release has classically been described as a secretory vesicle-mediated event. Yet, a limitation of the hypothesized vesicular GABA release from islets is the lack of expression of a vesicular GABA transporter in beta cells. Consequentially, GABA accumulates in the cytosol. Here we provide evidence that the human beta cell effluxes GABA from a cytosolic pool in a pulsatile manner, imposing a synchronizing rhythm on pulsatile insulin secretion. The volume regulatory anion channel (VRAC), functionally encoded by LRRC8A or Swell1, is critical for pulsatile GABA secretion. GABA content in beta cells is depleted and secretion is disrupted in islets from type 1 and type 2 diabetic patients, suggesting that loss of GABA as a synchronizing signal for hormone output may correlate with diabetes pathogenesis.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/s42255-019-0135-7
- PMID 32432213
- Persistent URL
- https://folia.unifr.ch/global/documents/194659
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