Hope for obesity and diabetes

HÉLÈNA KATZ | Two McGill researchers have found an enzyme in mice that could open the door to new treatments for type II diabetes and obesity in humans.

Working with a team from the pharmaceutical company Merck Frosst Canada, the Department of Biochemistry's Professor Michel Tremblay and post-doctoral research fellow Dr. Mounib Elchebly genetically altered white mice to suppress the gene responsible for the production of the PTP-1B enzyme.

Previous research had suggested that this enzyme could play a role in reducing insulin's ability to regulate blood sugar levels.

Tremblay and Elchebly found that the mice without the PTP-1B enzyme had significantly lower amounts of glucose in their blood after a meal than did normal mice and used only half of the amount of insulin normally required to regulate their blood sugar levels.

They also resisted weight gain despite being fed a diet consisting of 50 per cent fat.

The mice with the missing enzyme also remained healthy, Tremblay says.

"Either there are other ways to compensate for the absence of PTP-1B in the normal metabolism of the mouse or that enzyme's only purpose is to control glucose and insulin," he explains.

Since this enzyme works in similar ways in mice and humans, this latest finding could lead to the discovery of a drug that suppresses PTP-1B and treats both type II diabetes and obesity in humans.

"It's very important progress because it now orients us in the direction to go into," says Merck Frosst researcher Dr. Brian Kennedy.

More than one-third of people over the age of 40 suffer from obesity and that puts them at far greater risk for developing type II diabetes. Indeed, two-thirds of them will develop the illness. This group comprises 90 per cent of all diabetics. According to the World Health Organization, there were 35 million cases of type II diabetes worldwide in 1995.

Developing gradually, the illness occurs when the body's cells are unable to absorb enough blood sugar, or glucose. Unlike people with type I diabetes, those with type II do produce insulin, the hormone that controls the removal of glucose from the bloodstream and sends it to the body's cells. But their bodies don't react to its effects.

The insulin receptor of mice that lack the enzyme seemed to stay active longer than those of their normal, unaltered siblings. This could make them more sensitive to the effects of the hormone.

People with type II diabetes typically become less sensitive to insulin over time. This means that doses need to be increased to help them absorb glucose into their system. Yet too much insulin can be toxic. Long-term complications from the illness can include eye, kidney and heart damage.

Some of the current treatments for type II diabetes focus on drugs targeting a person's appetite, fat intake and liver function. This latest finding could improve treatment options, Tremblay says. "There isn't one way to deal with diabetes, but it gives doctors a panoply of options."

A drug that can suppress PTP-1B in humans means that people with type II diabetes won't need as much insulin to absorb glucose and regulate sugar levels in their body.

But Tremblay cautions that "we can't think there will be one magic bullet. One drug to do all that would be misleading."

Kennedy agrees that much research still needs to be done before their current findings can be applied to humans. "We've done this in a mouse and a mouse isn't a human being," he says. "We have a ways to go before we get to humans."

Getting there is a two-part process that involves finding a drug that suppresses the PTP-1B enzyme in mice and then testing it in humans.

The results of this latest research are reported in the March 5 issue of Science.

"There's no doubt that there will be interest in the scientific community to work on this enzyme," Tremblay says.

This research was the result of a three-year collaboration between the University's biochemistry laboratory and Kirkland-based Merck Frosst. Dean of Medicine Dr. Abraham Fuks comments that "it demonstrates the richness of industry and academic interaction."