Dr. Mohan in lab

Getting to the heart of diabetes complications

Tuesday, December 1, 2015by Elizabeth Allen

A simple combination of natural products with an element of aspirin is yielding clues in the fight against complications of diabetes.

Flexibility is important for our health, as we can feel when we stand and stretch. But along with being able to scratch that middle part of your back, flexibility benefits us in less obvious ways. In blood vessels, it means avoiding atherosclerosis, heart attacks and strokes.

Sumathy Mohan, Ph.D., is figuring out how to maintain vascular flexibility and, potentially, prevent one disease that is a risk factor for all of the above — diabetes.

Dr. Mohan, an associate professor in the Department of Pathology, focuses on a single layer of cells lining the interior of blood vessels called endothelial cells.

“I focus on the vascular complications of diabetes,” she said. “The complications are almost the same for Type 1 and Type 2 diabetes.”

Vascular endothelial cells form a selective barrier, allowing nutrients to pass through the vessel walls while forming a tight barrier to keep the blood itself pushing onward through the vessels.

“They’re the cells that see the blood flow first, so they see the blood components first,” Dr. Mohan said.

Keeping that layer flexible and responsive is the focus of Dr. Mohan’s work. To that end, she is researching the combination of salsalate, an aspirin-like product, with a natural product called L-arginine.

It’s about the flow

There is blood pressure, and then there is blood shear. The shear is the force exerted on the sides of the vessel walls as the blood flows through them. This force helps wipe the endothelium clear of things like LDL cholesterol and other inflammatory cells — anything that, if lodged in the blood vessel wall, can stiffen the vessel and build up the plaque that leads to heart problems and strokes.

Where the blood vessels branch, the blood shear force is lower. And that’s where the risks start to pile up.

“The low-shear places are present in a healthy person,” Dr. Mohan said. But with hyperglycemia — too much sugar in the blood — the excess sugar molecules change the chemistry of other molecules that tend to lodge in these vulnerable parts of vessel walls.

The aspirin cocktail

With funding from the National Institutes of Health, Dr. Mohan is investigating the effects of combining existing drugs and natural ingredients. She published a paper on the results in Laboratory Investigation in July.

“A naturally occurring amino acid combined with the active ingredient of aspirin helped vaso-relaxation in diabetic mice,” she said. “The aspirin alone has been shown to help but also has toxic effects. If the diabetic mice are fed only the L-arginine, they don’t get the benefit. Combining them enhances the benefit.”

Dr. Mohan had been doing this work for several years before she herself was diagnosed with diabetes.

“So now I can relate myself to my own work,” she said, smiling.

However, she’s not working for herself.

“Diabetes is slowly progressing throughout the globe,” Dr. Mohan said. “If we can help the younger generation who are prediabetic, many can avoid a lot of complications that are associated with diabetes.”