IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2013;5(2):91-101

Original Article
An autocrine γ-aminobutyric acid signaling system exists in pancreatic β-cell
progenitors of fetal and postnatal mice

Mary M Feng, Yun-Yan Xiang, Shuanglian Wang, Wei-Yang Lu

Department of Physiology and Pharmacology, Robarts Research Institute, University of Western Ontario, London ON, Canada

Received March 9, 2013; Accepted April 15, 2013; Epub May 27, 2013; Published June 15, 2013

Abstract: Gamma-aminobutyric acid (GABA) is produced and secreted by adult pancreatic β-cells, which also express GABA receptors
mediating autocrine signaling and regulating β-cell proliferation. However, whether the autocrine GABA signaling involves in β-cell
progenitor development or maturation remains uncertain. By means of immunohistochemistry we analyzed the expression profiles of
the GABA synthesizing enzyme glutamic acid decarboxylase (GAD) and the α1-subunit of type-A GABA receptor (GABAARα1) in the
pancreas of mice at embryonic day 15.5 (E15.5), E18.5, postnatal day 1 (P1) and P7. Our data showed that at E15.5 the pancreatic and
duodenum homeobox-1 (Pdx1) was expressed in the majority of cells in the developing pancreata. Notably, insulin immunoreactivity
was identified in a subpopulation of pancreatic cells with a high level of Pdx1 expression. About 80% of the high-level Pdx-1 expressing
cells in the pancreas expressed GAD and GABAARα1 at all pancreatic developmental stages. In contrast, only about 30% of the high-
level Pdx-1 expressing cells in the E15.5 pancreas expressed insulin; i.e., a large number of GAD/GABAARα1-expressing cells did not
express insulin at this early developmental stage. The expression level of GAD and GABAARα1 increased steadily, and progressively
more GAD/GABAARα1-expressing cells expressed insulin in the course of pancreatic development. These results suggest that 1)
GABA signaling proteins appear in β-cell progenitors prior to insulin expression; and 2) the increased expression of GABA signaling
proteins may be involved in β-cell progenitor maturation. (IJPPP1304001).

Keywords: γ-aminobutyric acid, GABA receptor, embryonic pancreas, β-cell progenitor

Address correspondence to: Dr. Wei-Yang Lu, Robarts Research Institute, University of Western Ontario, 100 Perth Drive, London,
Ontario Canada, N6A 5K8. Phone: 519-931-5777 ex 24282. E-mail: wlu53@uwo.ca