Authors:

Arabella Readey

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About Paper:

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that controls nervous cells' excitability. Pancreatic beta-cells have the largest concentration of GABA outside the brain, suggesting it greatly contributes to pancreatic islet function. Furthermore, islets from donors with diabetes have reduced GABA content in beta-cells. Studies showing the effect of exogenous GABA on insulin secretion are contradictory: GABA can be stimulatory or inhibitory depending on glucose concentrations. Our previous results using islets from conditional knockout mice lacking the GABA- synthesizing enzymes in pancreatic beta-cells (β-Gad1,2-/-) indicate that endogenous GABA can be inhibitory. We believe GABA's role in paracrine signaling may cause these different effects. Pancreatic islets express two types of GABA receptors, GABA-A-R (a ligand-gated Cl- channel) and GABA-B-R (a G Protein-coupled receptor). Our results using both agonists and antagonists of these receptor classes suggest GABA-A-R is inhibitory while GABA-B-R is stimulatory. Yet, further studies on the expression of GABA-A-R and GABA-B-R are needed to understand GABA's full effect on pancreatic islet function. Our objective is to identify the level of expression of GABA-A-R and GABA- B-R subunits in pancreatic alpha-, beta-, and delta-cells with available single-cell RNA sequencing transcriptomes, and to additionally compare their prevalence in β-Gad1,2-/- mice and wild-type mice via immunofluorescence. 155

Source:

University of Florida / 2024

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No topics listed

Co-authors:

Arabella Readey