Excessive loss of functional pancreatic beta-cell mass, mainly due to apoptosis, is a major factor in the development of hyperglycemia in both type 1 and type 2 diabetes (T1D and T2D). In T1D, beta-cells are destroyed by immunological mechanisms. In T2D, while metabolic factors are known to contribute to beta-cell failure and subsequent apoptosis, mounting evidence suggests that islet inflammation also plays an important role in the loss of beta-cell mass. Therefore, it is of great importance for clinical intervention to develop new therapies beta-Aminobutyric acid (GABA), a major neurotransmitter, is also produced by islet beta-cells, where it functions as an important intraislet transmitter in regulating islet-cell secretion and function. Importantly, recent studies performed in rodents, including in vivo studies of xenotransplanted human islets, reveal that GABA exerts beta-cell regenerative effects. Moreover, it protects beta-cells against apoptosis induced by cytokines, drugs, and other stresses, and has anti-inflammatory and immunoregulatory activities. It ameliorates the manifestations of diabetes in preclinical models, suggesting potential applications for the treatment of diabetic patients. This review outlines the actions of GABA relevant to beta-cell regeneration, including its signaling mechanisms and potential interactions with other mediators. These studies increase our understanding of the regenerative processes of pancreatic beta-cells, and help pave the way for the development of regenerative medicine for diabetes.
[1]Fudan Univ, Huashan Hosp, Dept Endocrinol & Metab, Med Coll, Shanghai, Peoples R China.
[2]St Michaels Hosp, Div Endocrinol & Metab, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada.
[3]Univ Toronto, Fac Med, Dept Physiol, Toronto, ON, Canada.
[4]Univ Toronto, Fac Med, Dept Med, Toronto, ON, Canada.
[5]Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[6]St Michaels Hosp, Keenan Res Ctr Biomed Sci, Dept Lab Med, Toronto, ON, Canada.
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