GABA promotes human β-cell proliferation and modulates glucose homeostasis

Diabetes. 2014 Dec;63(12):4197-205. doi: 10.2337/db14-0153. Epub 2014 Jul 9.


γ-Aminobutyric acid (GABA) exerts protective and regenerative effects on mouse islet β-cells. However, in humans it is unknown whether it can increase β-cell mass and improve glucose homeostasis. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-γ mice with streptozotocin-induced diabetes. GABA treatment increased grafted β-cell proliferation, while decreasing apoptosis, leading to enhanced β-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 β-cell proliferation and survival. Our findings suggest that GABA regulates human β-cell mass and may be beneficial for the treatment of diabetes or improvement of islet transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cell Proliferation / drug effects*
  • Diabetes Mellitus, Experimental*
  • GABA Agents / pharmacology*
  • Glucagon / drug effects
  • Homeostasis / drug effects
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans Transplantation*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • gamma-Aminobutyric Acid / pharmacology*


  • Blood Glucose
  • GABA Agents
  • Insulin
  • gamma-Aminobutyric Acid
  • Glucagon