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

γ-Aminobutyric acid (GABA) has been shown to inhibit apoptosis of rodent β-cells in vitro. In this study, we show that activation of [GABA.sub.A] receptors ([GABA.sub.A]-RS) or [GABA.sub.B]-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 [GABA.sub.A]-R- or [GABA.sub.B]-R-specific agonist, inhibited human β-cell apoptosis following islet transplantation into NOD/scid mice. Accordingly, activation of [GABA.sub.A]-RS and/or [GABA.sub.B]-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 [GABA.sub.A]-R and [GABA.sub.B]-R activation. Hence, GABA regulates both the survival and replication of human [3-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 [3-cell survival following human islet transplantation and increasing [3-cells in patients with diabetes. Diabetes 62:3760-3765, 2013
A central focus of research in the type 1 diabetes (T1D) field is to develop ways to safely improve [3-cell survival and function and promote their replication. The addition of [...]