UNLV Magazine | Spring 2005 | Backfiring Biology

There’s more than one way to skin a cat, as the saying goes. In the university world this translates into different approaches to the same scientific problem. Take the alarming rise in diabetes among Native Americans. On one side of campus, molecular biologists are trying to pinpoint the genes that predispose the Pima Indians to diabetes. A few buildings away, an anthropologist believes there is a strong link to socio-political factors. Which one is right? The researchers are quick to point out that perhaps there’s fact on both sides. “Different disciplines take different approaches,” says Deboarah Hoshizaki, a biological sciences professor. “It’s the debate that the different approaches can spark that leads to real discoveries.”

It’s in the Genes

The unusual hardiness of the Pima Indians of Arizona is now the same trait that threatens their lives. Their genetic makeup enables them to store fat efficiently, something that served them well when extreme privation was common in the barren Southwest. But when the Pima began to adopt modern diets, their survival mechanism backfired. Researchers believe their efficient fat-storage mechanism resulted in obesity and an alarming rise in type II diabetes.

Now, two UNLV biology professors are researching the specific genes that promote fat storage. Deborah Hoshizaki and Allen Gibbs are working with fruit flies, which are ideal candidates for genetic research because they breed quickly and have short life cycles. “With flies, we get a new generation every three weeks,” says Gibbs.

In the first phase of their research, Gibbs fed the flies water, but no food. The flies that survived longest on the starvation regimen were then mated to each other to produce super-starvation-resistant flies. Not surprisingly, the flies became obese when fed a normal regimen. This process enabled Gibbs to locate the genes in the flies that appear to act together to produce the same kind of starvation resistance seen in the Pima.

“Now that Allen has identified the genes that might be important, I will be involved in testing each gene to see which ones are really at work here,” says Hoshizaki.

The next step, which will be left to other researchers, would be to find human counterparts to the starvationresistant genes found in the flies. “If we understand the pathway that is leading to this over-storage of fat in people, then pharmaceutical companies can design drugs that could counteract the predisposition to gain weight,” she says. “These drugs might not only help the Pima, but they might also help others in the general population who have a milder version of the same problem.”

The Link to Malnutrition

For decades, scientists have theorized that genetics play the critical role in the epidemic of type II diabetes among the Pima Indians, where more than 50 percent of the adults over age 35 have the disease.

“These are the highest type II rates in the world. The question is, ‘Why?’” anthropology professor Daniel Benyshek says. “The answer so far has been this thrifty gene idea. In my view, genes likely play some role, but I think something else of equal — if not greater — importance is at work too.”

The evidence for Benyshek’s theory comes from animal and human studies done since the early 1990s that suggest malnutrition among pregnant mothers can predispose their offspring to the disease. He believes the malnutrition sets in motion a cycle in which the predisposition to type II diabetes can be transmitted from generation to generation.

Low birth weight is a sign of maternal malnutrition. Benyshek cites a study on British adults who were underweight when they were born in the 1930s and ’40s. Researchers later found they had a high incidence of type II diabetes. Studies with rats, in which pregnant mothers were malnourished, also found a high incidence of type II diabetes in their offspring.

For subsequent generations, Benyshek thinks a different mechanism is at work. Diabetic mothers have high blood-sugar levels if the disease it not controlled, and this can affect the biological development of fetuses and predispose them to get type II diabetes, he says. “Once it gets started, it can be propagated from generation to generation. That’s the bottom line.”

With the Pima, he suggests the malnourishment occurred during the period of extreme privation that followed the late 19th century settlement of the American West. The Pima had been successful irrigation farmers in Arizona, but when the settlers arrived, the Pima lost much of their land and almost all their irrigation water. This plunged the tribe into economic darkness, Benyshek says. “They couldn’t grow their food and they couldn’t afford to buy it. People were literally starving to death.”

When the deprivation began to end in the 1950s, he says, the pendulum swung toward obesity, a high risk factor for type II diabetes, and incidence of the disease began to soar.

Benyshek theorizes that it may be possible to break the cycle by controlling blood-sugar levels during pregnancy through diet, exercise, and medication. He is now testing his thesis on rats. “We’ll know the results in December,” he says. “If the animal tests are promising, the next thing to do is find a way to test it with humans to see if we can end the cycle.”