Antioxidants:

The body’s warriors against the effects of diabetes

In the battle against diabetes, researchers are still searching for the ultimate warrior:  A material that will prevent the chronic effects of diabetes on the body.  A researcher at the University of North Dakota (UND) hopes that he and his co-workers have found just such a warrior.

The Diabetes Dilemma

Most of the food we eat is turned into sugar, or glucose, for our bodies to use as energy. The pancreas, an organ that lies near the stomach, makes a hormone called insulin to help glucose get out of our blood and into our cells to be used as energy.  The body of a person with diabetes either does not make enough insulin or cannot use its own insulin as well as it should. This causes sugar to build up in the blood, or diabetes.

According to the Centers for Disease Control and Prevention (CDC), diabetes is the sixth leading cause of death in the United States.  Just over six percent or 18.2 million people in the U.S. have diabetes. More than a quarter of those people have not been diagnosed.

The long-term effects of having too much sugar in the blood, or hyperglycemia, can be chronic complications in four main areas of the body:  the eyes, nervous system, heart and kidneys.

Killing the Kidneys

The most recent research of Edward Carlson, Ph.D. ’70, Chester Fritz Distinguished Professor and chair of the anatomy and cell biology department at UND, looks at the long-term effects of diabetes on the small blood vessels of the kidney.

Although these tiny blood vessels, or capillaries, are only a tenth the diameter of a human hair, they play an important role of fencing protein in the blood stream.  The capillary walls of the kidney include a tube-like structure called the basement membrane, which works as a filter allowing the blood to jettison things that are not needed and keep what is.  However, long-term hyperglycemia caused by diabetes can start to make the basement membrane rigid, brittle and more permeable, allowing protein to leave the capillary.  This results in renal disease, or disease of the kidney.

Diabetes is the leading cause of end-stage renal disease, accounting for 44 percent of new cases, according to the CDC.  In 2001, nearly 143,000 people with end-stage renal disease due to diabetes were living on chronic dialysis or with a kidney transplant.

Carlson and his research partner, former UND pharmacology chair Paul Epstein, Ph.D., are looking at ways to counteract the effect high blood sugar has on the basement membrane of kidney capillaries. 

“We can estimate your age by looking at your capillaries,” explains Carlson.  “Diabetes is sometimes called the disease of premature aging.  The capillaries of a person with diabetes will look much older than they actually are.” 

Antioxidants Attack

Carlson and Epstein are studying the effects of antioxidants on this premature aging of the capillaries, which causes them to become rigid and more permeable much sooner than they should.  This premature aging of the capillaries is caused by an unusually high level of free radicals in the bodies of people with diabetes. 

Epstein, an animal geneticist who is now professor of pediatrics at the University of Louisville, has developed two types of mice for their work.  The first type of mouse is born with diabetes.  The second kind of mouse is also diabetic, but it also creates more antioxidants than a typical mouse. 

Significantly, in the diabetic mouse that creates more antioxidants than usual, basement membranes are protected against increased permeability and other characteristics of advanced diabetic kidney disease.  Carlson and his students are examining the cells and basement membranes in these genetically engineered mouse models using the UND medical school’s electron microscope. They have demonstrated several new findings including changes in basement membrane thickness as well as altered cell shape and number.

“It seems that the excess antioxidants are eating away at the free radicals that cause the filtering mechanism in the kidney to age prematurely,” explained Carlson. 

Carlson hopes that their work will inspire clinical trials in which people with diabetes could be treated with antioxidants and, hopefully, have the same results as these mice. 

“We hope that it can be shown that antioxidants successfully prevent the chronic complications of diabetes,”

he said. 

“This is truly exciting work,” said Carlson.  “It is so much fun.  I get up every morning and I can hardly wait to get here to see what is happening now.”

-Amanda Scurry

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