December 18, 1998

Granner two-time MERIT winner

Granner two-time MERIT winner

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Dr. Daryl Granner

Receiving a Method to Extend Research in Time (MERIT) grant from the NIH is a great honor for any researcher, but one VUMC scientist has received two of the coveted awards for the same avenue of research.

MERIT grants are given by the National Institutes of Health (NIH) to investigators whose research appears to have the best chance to produces results that will impact the health of human beings. They represent five years of continuous funding without resubmitting applications or proposals.

"MERIT grants are a great honor for both the laboratory as a whole and for the investigator," said Dr. Daryl K. Granner, Joe C. Davis Professor of Biomedical Science and director of the Vanderbilt Diabetes Center.

"It is a pleasure to know that the NIH believes the research we are conducting here has so much promise."

The major benefit of a MERIT grant is that it lasts for five years instead of the usual two. This allows the researcher several more years to dedicate time to actual research instead of the administrative tasks of writing grant proposals.

"MERIT grants are one of the best ways the NIH has of allowing researchers to get all that they can from their research," said Granner.

Granner's research focuses on the phosphoenolpyruvate carboxykinase (PEPCK) gene, a complete analysis of which could unlock the metabolic mechanisms of glucose production in the liver. Many hormones, including insulin, regulate the PEPCK gene.

"The role of insulin is to decrease PEPCK and thus restrain glucose release so that the blood sugar does not go too high," said Granner.

Recent studies indicate that transgenic mice that over-express the gene develop a disease similar to diabetes. There is also evidence that the gene is not normally regulated by insulin in diabetes.

Drug companies are currently studying this gene to develop drugs to manipulate its action.

"The regulation of this gene, particularly by insulin, has been a particularly elusive target. We have been looking for it for quite some time," said Granner.

"One of the reasons we are so interested in the PEPCK gene is that we believe a portion of it to be controlled by a mechanism we have called a metabolic control domain."

A metabolic control domain is a complex switch that assimilates several environmental cues and sets the activity of the PEPCK gene. The setting then determines glucose production in the liver.

If this PEPCK gene metabolic control domain does set the body's glucose production "clock," then discovering ways to manipulate the gene could provide scientists with a way to somehow reset the glucose production system to a lower level.

However, a genetic keystone that could turn down the production of glucose in the body is a long way off, warned Granner.

"We know that his gene has profound effects on the disease but it is a long way from here to a treatment of the disease."