Mechanism and Effects of Pulsatile GABA Secretion from Cytosolic Pools in the Human Beta Cell

Overview

Journal Nat Metab

Publisher Springer Nature

Specialty Endocrinology

Date 2020 May 21

PMID 32432213

Citations 47

Authors

Danusa Menegaz

D Walker Hagan

Joana Almaca

Chiara Cianciaruso

Rayner Rodriguez-Diaz

Judith Molina

Robert M Dolan

Matthew W Becker

Petra C Schwalie

Rita Nano

Fanny Lebreton

Chen Kang

Rajan Sah

Herbert Y Gaisano

Per-Olof Berggren

Steinunn Baekkeskov

Alejandro Caicedo

Edward A Phelps

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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