Research published in February 2020 in Diabetes Research News describes the potentially important role of gamma amino-butyric acid (GABA) in the modulation and regulation of insulin.

Edward Phelps, PhD, an assistant professor in the J. Crayton Pruitt Family Department of Biomedical Engineering at University of Florida, and his interdisciplinary research team explored the mechanism whereby GABA is released from the pancreatic beta cells in a coordinated, synchronized manner with insulin to stabilize insulin levels. GABA is thought to be released from cells in the body’s effort to “calm” and “prepare” the cells for the next wave(s) of insulin secretion, and in the presence of absent or diminished GABA, there would be increased risk of dysfunction and/or inflammation associated with both type 1 and type 2 diabetes. 

Dr. Phelps and his colleagues published the original paper in November 2019 in Nature Metabolism, describing the method they used to measure the release from beta cells in the pancreas. Employing a process that included both GABA biosensor cell assays and high-performance liquid chromatography, the team measured the release of GABA from human pancreatic islet cells with visible fluorescence observed by confocal microscopy in a biosensor when GABA was released. 

According to a press release from the Herbert Wertheim College of Engineering, Dr. Phelps noted, “There is a channel between the interior of the beta cell and the extracellular space, which we thought was worth investigating.” He added, “The volume regulatory anion channel (VRAC) is known for another purpose. It is used to help cells maintain their shape by keeping the osmotic pressure inside and outside the cell in equilibrium. When this balance is disturbed and the cell shape changes, small organic chemicals known as osmolytes are expelled from the cell via the VRAC channel to help the cell regain its shape. When we artificially opened this channel in beta cells using low saline, we found that this channel also transports GABA.” 

Based on this research, Dr. Phelps and his team concluded that GABA release occurs in pulses with a frequency similar to that of normal pulsatile insulin secretion and regulates the interval of insulin secretion. Further, GABA is released independently of glucose concentration, and GABA receptors, when activated, regulate beta-cell activity via autocrine signaling pathways.

“As other researchers build on what we have done and show reproducible results, we will open up totally new areas of biomedical research that scientists can investigate, including possible new treatments for diabetes and potential defense against autoimmune activity,” Dr. Phelps concluded.

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