| First Author | Purwana I | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 12 | Pages | 4197-205 |
| PubMed ID | 25008178 | Mgi Jnum | J:230144 |
| Mgi Id | MGI:5755562 | Doi | 10.2337/db14-0153 |
| Citation | Purwana I, et al. (2014) GABA promotes human beta-cell proliferation and modulates glucose homeostasis. Diabetes 63(12):4197-205 |
| abstractText | gamma-Aminobutyric acid (GABA) exerts protective and regenerative effects on mouse islet beta-cells. However, in humans it is unknown whether it can increase beta-cell mass and improve glucose homeostasis. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-gamma mice with streptozotocin-induced diabetes. GABA treatment increased grafted beta-cell proliferation, while decreasing apoptosis, leading to enhanced beta-cell mass. This was associated with increased circulating human insulin and reduced glucagon levels. Importantly, GABA administration lowered blood glucose levels and improved glucose excursion rates. We investigated GABA receptor expression and signaling mechanisms. In human islets, GABA activated a calcium-dependent signaling pathway through both GABA A receptor and GABA B receptor. This activated the phosphatidylinositol 3-kinase-Akt and CREB-IRS-2 signaling pathways that convey GABA signals responsible for beta-cell proliferation and survival. Our findings suggest that GABA regulates human beta-cell mass and may be beneficial for the treatment of diabetes or improvement of islet transplantation. |
