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.”
- 30 -
News for
the week of Jan
30 – Feb 3
