Beta cell secreted GABA sets appropriate insulin secretion by modulating islet calcium oscillations.

ABSTRACT:

Objectives

Gamma-aminobutyric acid (GABA) is produced in pancreatic beta cells and is implicated in modulating islet function, yet its precise physiological role remains uncertain. This study aimed to determine the function of endogenous beta cell-derived GABA on insulin secretion and islet calcium dynamics by developing a conditional beta cell-specific knockout of GABA-synthesizing enzymes (GAD65 and GAD67).

Methods

Conditional knockout mice (Gad^βKO) lacking both GAD65 and GAD67 specifically in pancreatic beta cells were generated. Glucose-stimulated insulin secretion was measured in isolated islets and in vivo and islet Ca²⁺ oscillations were recorded using calcium imaging. The effects of GABA and its receptor agonists/antagonists were tested under va

SUBMITTER: Ferreira SM 

PROVIDER: S-EPMC12603775 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature