DRI Researchers Identify Important Regulator of Blood Sugar, Possible Therapeutic Target
Miami, FL (June, 2008) -- Researchers from the Diabetes Research Institute at the University of Miami Leonard M. Miller School of Medicine and Karolinska Institutet in Stockholm, Sweden, have identified an important mechanism that helps the body regulate blood sugar concentration – a novel finding that could help treat patients with diabetes.
The study is important enough to be featured on the cover of the June 2008 issue of the prestigious journal Cell Metabolism.
In terms of regulation of overall blood sugar concentration, there are two types of hormone secreting islet cells in the pancreas that are of specific importance, namely betacells, which produce insulin and alphacells, which produce glucagon.
Insulin triggers cells to absorb glucose from the blood, and glucagon triggers the production of more glucose into the blood. Both insulin and glucagon release into the blood are disturbed in patients with diabetes.
Just how the body regulated the correct amount of glucagon wasn’t clear until now, says Per-Olof Berggren, Ph.D., of the Diabetes Research Institute in Miami and Karolinska Institutet in Stcokholm and the senior investigator of the study. Over Cabrera and collaborators found that, in addition to glucagon, pancreatic alpha cells also release glutamate, a neurotransmitter which facilitates the release of glucagon.
“We learned that glutamate acts as a positive signal that instructs alpha cells to speed up glucagon secretion in order to prevent glucose levels from falling too low,” said Alejandro Caicedo, Ph.D., research assistant professor at the Diabetes Research Institute and one of the authors of the study.
That process prevents hypoglycemia, which is a serious drop in blood sugar. The researchers were able to show that glutamate drives a feedback system for glucagon release in the alpha cells. The results establish glutamate as a bona fide autocrine signaling molecule, the mechanism by which human islets secrete the appropriate level of glucagon.
These new findings may help clarify why alpha cells do not also work the way they should in diabetes to prevent hypoglycemia.
The next step is to see whether this feedback loop can be exploited to treat patients with diabetes. The research teams in Miami and Stockholm are currently conducting experiments to test the idea that the glutamate receptors involved in the feedback system can be pharmacological targets for intervention in diabetes.
Jeanne Antol Krull