Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell
| Autor: | Matthew W. Becker, Judith Molina, Joana Almaça, Robert M. Dolan, Rayner Rodriguez-Diaz, Alejandro Caicedo, Rita Nano, Rajan Sah, Chen Kang, Herbert Y. Gaisano, Chiara Cianciaruso, Danusa Menegaz, Edward A. Phelps, Per Olof Berggren, D. Walker Hagan, Steinunn Baekkeskov, Petra C. Schwalie, Fanny Lebreton |
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| Rok vydání: | 2019 |
| Předmět: |
Pulsatile insulin
Endocrinology Diabetes and Metabolism aminobutyric-acid gaba essential component Autoimmune Disease Article pancreatic-islet cells Paracrine signalling Cytosol golgi membranes alpha-cells Physiology (medical) Insulin-Secreting Cells Internal Medicine Diabetes Mellitus Humans Homeostasis 2.1 Biological and endogenous factors Secretion glucose-inhibition Aetiology Autocrine signalling gamma-Aminobutyric Acid Metabolic and endocrine geography geography.geographical_feature_category ddc:617 Chemistry Diabetes Glucagon secretion Neurosciences Cell Biology Islet Cell biology substrate-specificity Diabetes Mellitus Type 1 nervous system Diabetes Mellitus Type 2 synaptic-like microvesicles glucagon-secretion Beta cell Type 2 insulin-secretion Subcellular Fractions Type 1 |
| Zdroj: | Nature metabolism, vol 1, iss 11 Nature metabolism Nature Metabolism, Vol. 1, No 11 (2019) pp. 1110-1126 |
| ISSN: | 2522-5812 |
| Popis: | Pancreatic beta cells synthesize and secrete the neurotransmitter GABA (gamma-aminobutyric acid) 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, 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 patients with type 1 and type 2 diabetes, suggesting that loss of GABA as a synchronizing signal for hormone output may correlate with diabetes pathogenesis. |
| Databáze: | OpenAIRE |
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