Glutamate toxicity causes insulin producing beta cell death
Scientists have made an important discovery about how beta cells in the pancreas that produce insulin die, leading to diabetes. The researchers say it is alpha cells that create a toxic imbalance by releasing a hormone called glutamate, leading to beta cell death.
Glutamate behaves like an adversary to pancreatic beta cells
Glutamate plays an important role in the body's metabolism and acts as a neurotransmitter in the brain but is also released by the pancreas and found in bones. Alpha cells also release glucagon that raises blood sugar levels, along with glutamate.
According to Franco Folli, M.D., Ph.D., professor of medicine/diabetes at The University of Texas Health Science Center at San Antonio who conducted the study with Carla Perego, Ph.D., assistant professor of physiology at the University of Milan, "Our study shows that neighboring cells called alpha cells can behave like adversaries for beta cells." He says the finding was unexpected. "In a situation where there is an imbalance toward more alpha cells and fewer beta cells, as in Type 1 and Type 2 diabetes, this could result in further beta cell destruction."
Drs. Perego and Folli explain destruction of insulin secreting beta cells by glutamate was not previously known. During the study, the researchers also found a protein that regulates glutamate that can protect beta cells from death called GLT1.
"GLT1 is like a thermostat controlling the microenvironment of beta cells with respect to glutamate concentration," Dr. Perego said.
"The vicious cycle in diabetes is that there are several substances that have been shown, also by us, to be toxic to beta cells," Dr. Folli said. "And now we have found a new one, glutamate."
Now that the researchers understand how insulin cells die, they are working on a new test that can detect glutamate toxicity, in hopes of finding a way to slow the process.
Journal of Biological Chemistry: doi: 10.1074/jbc.M110.183517