Skip to main content
eScholarship
Open Access Publications from the University of California

UCLA

UCLA Previously Published Works bannerUCLA

γ-Aminobutyric acid regulates both the survival and replication of human β-cells.

  • Author(s): Tian, Jide
  • Dang, Hoa
  • Chen, Zheying
  • Guan, Alice
  • Jin, Yingli
  • Atkinson, Mark A
  • Kaufman, Daniel L
  • et al.

Published Web Location

https://doi.org/10.2337/db13-0931
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View