Fat Rats Shed Light on Diabetes

K.C. Hayes
Mike Lovett
K.C. Hayes

Diabetes is a scourge of modern life. Of the nearly 26 million Americans living with the condition, more than 90 percent have Type 2, the chronic disease associated with a cascade of health woes — notably heart disease, stroke, high blood pressure and obesity. Now one diminutive rodent is proving to be a mighty partner in the search to understand better the roles dietary fat and sugar play in this national plague.

Turns out, says biology professor and lipid expert K.C. Hayes, the Nile rat, denizen of African savannas and the Nile River, can grow and gain weight too quickly on an unrestricted diet, developing diabetes in much the same way humans do. The rat becomes diabetic on a much more accelerated schedule of weeks or months (in humans it can take decades), and sometimes, but not always, as a consequence of obesity. These two characteristics have enabled Hayes and colleagues to detect two different diabetes triggers, fat and glucose.

The director of the Foster Biomedical Research Laboratories at Brandeis, Hayes has devoted more than 40 years to understanding how dietary fat is metabolized and what kinds of fat promote heart health. His biggest claim to fame is as director of the research behind the popular family of Smart Balance blended-fat products, some of which also use plant phytosterols in buttery spreads and related products to help reduce cholesterol. Piggybacking on this research, his lab has successfully refined phytosterol technologies to produce cholesterol-lowering soy and cow’s milk in recent clinical trials at Brandeis.

Hayes has always been interested not just in reducing people’s cholesterol, but in disease prevention as well. His work with Nile rats began about five years ago, and since then Hayes and his research team have been studying the difference between sugar- and fat-induced forms of diabetes as modulators of insulin dynamics. As far as Hayes knows, he is the first scientist to study the Nile rat for its susceptibility to diabetes. What makes this rat a perfect study animal is its tendency to develop insulin resistance, high blood pressure, increased abdominal fat, and high triglycerides as a result of disturbed insulin metabolism — all health risks associated with diabetes and heart disease in humans.

Hayes has discovered how dietary fat and glucose may target muscle or insulin-secreting beta cells and initiate diabetes. Insulin, a hormone produced by the pancreas, regulates how the body converts sugar (glucose) into energy in tissues. A high glucose diet in any species puts an extreme burden on the pancreatic beta cells to produce more insulin. Eventually, this can lead to a production rate of insulin that cannot be sustained, damaging the beta cells and resulting in lower insulin production and Type 2 diabetes. By contrast, a high-fat diet makes it difficult for muscle cells to metabolize fatty acids; as a result, these cells reject further glucose uptake, leading to insulin resistance and eventually inducing diabetes as well.

As a result of observing how fat and glucose interact with insulin, Hayes has determined that they can act separately in different cell types to induce diabetes, a novel finding. The team is close to finding the optimal diet to prevent diabetes in these animals, an important step in determining the best anti-diabetes diet for humans. What’s on the menu? Limited calories and glucose; lots of essential fatty acids, such as those found in vegetable and fish oils; and high-fiber foods, including beans, broccoli, eggplant, okra and oatmeal, all of which prevent glucose from being absorbed too quickly.

Penny Schwartz is a freelance writer in Newton, Mass.

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