by Kirsten Brown

For an alarmingly high number of Ohioans, diabetes has become a critical concern. In fact, from Pennsylvania to North Carolina, an unusual proportion of Americans face serious complications from diabetes. Fortunately, a recent grant awarded to Sharon Inman, Ph.D., and Felicia Nowak, M.D., Ph.D., has paved the way for an experiment that may offer hope.

Nowak, an associate professor of molecular endocrinology, and Inman, an assistant professor of physiology, are teaming up to conduct an experiment where the results could provide a solution to kidney failure, a common consequence of diabetes.

“Diabetes is reaching epidemic proportions in the Appalachia,” Inman says. “So we’re looking at a Type 2 diabetes model, which is very prevalent in the Appalachia area. This is due to a high rate of obesity. About 40 percent of diabetics will end up with kidney disease, which could be fatal, as diabetes is a leading cause of renal failure.”

And according to Inman, the answer to kidney failure may lie in antioxidants.

“We know there are some oxidative stress-cycles that enter in during diabetic nephropathy,” she says, “so antioxidants should take that away.”

The grant, awarded by the National Institutes of Health for $220,500, will fund research studying the effects of an antioxidant-supplemented diet and a diet with normal levels of antioxidants on the kidneys of diabetic rats.

“What we want to see,” Inman says, “is whether the antioxidant diet will slow the progression of the diabetic nephropathy and improve kidney function in the rats.”

Diabetic nephropathy, Inman explains, is kidney disease arising from diabetes. In the first stage, the blood vessels dilate, causing increased blood flow and therefore increased glomular filtration rate (GFR).

“So that wear and tear on the glomular membrane eventually destroys the kidney, so they lose their kidney function,” Inman says. “What happens is the nephrons of the kidneys begin to fail, and when so many of them fail this causes hypofiltration, which is low blood flow in the kidney and low GFRs.”

Once this occurs, the damage is irreversible, Inman says.

Using the antioxidant diet as their independent variable, the two researchers will explore its effects on kidney function and nitric oxide synthase (NOS) isoenzymes in the kidney tissue, among other factors.

“We think that we want to see what happens with the different nitric oxide synthase enzymes during the progression of diabetic nephropathy,” Inman says.

From their research, they could develop an antioxidant drug to prevent kidney failure, or even something as simple as a formula for a diet that’s high in antioxidants.

“Antioxidants could become a key part of the diet that doctors put diabetic patients on,” Inman says.

The OU-COMers’ scientific credentials lend themselves to this research problem.

“The idea for the project grew out of my background in endocrinology and Dr. Inman’s interest in mechanisms of renal injury,” Nowak says.

Inman, who specializes in the studies of ischemia/reperfusion injury in kidney transplantation, has studied in kidney damage caused by blood flow problems. Similarly, Nowak’s research provided the necessary framework for studying NOS isoenzymes.

“It is very helpful for me to have her look at the isoenzymes, because she knows molecular techniques, and I just do physiology in my lab,” Inman says of Nowak. “We want to compare how those isoenzymes change during diabetic nephropathy.”

“Can an antioxidant-supplemented diet ameliorate changes in oxidative metabolism that can lead to the development of Type 2 diabetes and associated renal injury?” Nowak poses. “Because of the data showing a rapid increase in type 2 diabetes associated with obesity, we decided to ask the question in an animal model of this disorder. The first step was to find a suitable animal model.”

In the end, the two OU-COM scientists selected the obese Zucker rat, because of its genetically inherited obesity and, thus, tendency toward kidney failure.

“It’s a good model, and they do get very fat,” Inman says. “The fatty tissue that is in these animals is tremendous, so they get very obese and end up with very high glucose levels.”

Next they designed the antioxidant supplemented diet. Nowak and Inman then constructed their experimental design, which will include an exploration of whether gender may affect the progression of diabetic nephropathy by using equal numbers of male and female rats. Finally, they presented their research goals in a grant proposal that was reviewed by experts in the field.

“This entire process took several hours every day over a period of five months,” Nowak says.

If Inman and Nowak produce encouraging results in the next two years, the grant will be up for renewal in January 2008.

“The original grant application was for two years of funding,” Nowak says. “A satisfactory progress report on the first year is required to qualify for the second year of funding — called a non-competitive renewal. After that, a new grant can be submitted on the same project.”

Overall, both scientists look with anticipation toward beginning the research. As Nowak says it is a great opportunity because of the research’s “possible future impact for prevention and treatment of Type 2 diabetes.”

If successful, Inman and Nowak will be pioneering the field of antioxidants as a defense against damage done by diabetes.

“We’re pretty much the first,” Inman says. “We’re excited to see how the results turn out.”