γ-Aminobutyric Acid Regulates Both the Survival and Replication of Human β-Cells

  1. Daniel L. Kaufman1
  1. 1Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California
  2. 2Departments of Pathology and Pediatrics, University of Florida, Gainesville, Florida
  1. Corresponding author: Daniel L. Kaufman, dkaufman{at}mednet.ucla.edu, or Jide Tian, jtian{at}mednet.ucla.edu.

Abstract

γ-Aminobutyric acid (GABA) has been shown to inhibit apoptosis of rodent β-cells in vitro. In this study, we show that activation of GABAA receptors (GABAA-Rs) or GABAB-Rs significantly inhibits oxidative stress–related β-cell apoptosis and preserves pancreatic β-cells in streptozotocin-rendered hyperglycemic mice. Moreover, treatment with GABA, or a GABAA-R– or GABAB-R–specific agonist, inhibited human β-cell apoptosis following islet transplantation into NOD/scid mice. Accordingly, activation of GABAA-Rs and/or GABAB-Rs may be a useful adjunct therapy for human islet transplantation. GABA-R agonists also promoted β-cell replication in hyperglycemic mice. While a number of agents can promote rodent β-cell replication, most fail to provide similar activities with human β-cells. In this study, we show that GABA administration promotes β-cell replication and functional recovery in human islets following implantation into NOD/scid mice. Human β-cell replication was induced by both GABAA-R and GABAB-R activation. Hence, GABA regulates both the survival and replication of human β-cells. These actions, together with the anti-inflammatory properties of GABA, suggest that modulation of peripheral GABA-Rs may represent a promising new therapeutic strategy for improving β-cell survival following human islet transplantation and increasing β-cells in patients with diabetes.

  • Received June 13, 2013.
  • Accepted July 16, 2013.

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  1. Diabetes vol. 62 no. 11 3760-3765
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