The scientists injected mice with colon cancer cells to mimic one of several digestive-system cancers strongly associated with the development of cachexia. Less than two weeks after the cancer started growing, these mice had become insulin resistant. Control mice without tumors had normal insulin sensitivity. Insulin resistance means that the presence of insulin does not initiate the transfer of sugar, or glucose, from the blood into the tissues, where it is used for energy.
Just three days later, the mice with cancer weighed, on average, 20 percent less than control mice with no tumors; weight loss of at least 5 percent is considered to be a sign of cachexia in humans. By day 19, the total muscle weight in mice with cancer decreased by 29 percent and the weight of their fat tissue dropped by 73 percent. Such rapid loss of muscle and fat indicated these mice had indeed developed cachexia.
"These data provide evidence that in mice with colon cancer tumors, insulin resistance may be involved in the development of cachexia rather than occur as a result of cachexia," Belury said. "And the key here is that people and animals with cachexia do not want to be losing weight. They can eat more and it doesn't matter. There's something internally that's driving this fat and muscle loss."
In the second study, the scientists tested whether rosiglitazone could "rescue" the insulin resistance in mice with colon cancer.
In this study, mice were fed a high-fat diet and randomized into three groups: mice with and without tumors receiving a saline solution as a control, and mice with tumors treated with daily injections of rosiglitazone.
Within eight days, the mice with cancer receiving the rosiglitazone showed more sensitivity to insulin than did the mice with tumors that received no medication. The insulin sensitivity of the medicated mice matched that of mice without tumors.
|Contact: Martha Belury|
Ohio State University