γ-Aminobutyric Acid Regulates Both the Survival and Replication of Human β-Cells
- Jide Tian1⇑,
- Hoa Dang1,
- Zheying Chen1,
- Alice Guan1,
- Yingli Jin1,
- Mark A. Atkinson2 and
- Daniel L. Kaufman1⇑
- 1Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California
- 2Departments of Pathology and Pediatrics, University of Florida, Gainesville, Florida
- Corresponding author: Daniel L. Kaufman, , or Jide Tian, .
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.
- © 2013 by the American Diabetes Association.
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