Diabetes drug shows promise in fighting lethal cancer complication
And in an animal study, a diabetes drug that promotes insulin sensitivity, slow the progression of muscle atrophy and loss of fat, the main consequences of a syndrome called cachexia in mice with colon cancer tumors.
Although it is unknown whether this drug, rosiglitazone, has the potential to prevent cancer cachexia in humans, the finding led researchers to believe that insulin resistance in cancer patients could stop improving their quality of life.
Research suggests that cachexia is responsible for between one fifth and one third of all cancer deaths.
The insulin resistance and cachexia both seem to be connected to inflammation-induced tumors either themselves or by secretions from tumors that trigger an immune response, researchers say.
“Insulin resistance generally continues to obesity. In this case, which precedes fat loss uncontrollable,” said Martha Belury, lead study author and professor of human nutrition at Ohio State University. “The insulin resistance is the process we have identified which occurs soon after forming tumors. So if we can change that part of the disease, might be able to change career progression and the speed with fat and muscles are lost. That is our goal. ”
The research appears online and is scheduled for future print publication in the International Journal of Cancer.
Belury and colleagues performed two experiments. In the first, researchers tried to demonstrate that the animals developed insulin resistance, shortly after they developed cancer before the muscles and fat loss was evident. In the second, which tested the effectiveness of insulin sensitizing drug rosiglitazone against this same tendency toward insulin resistance.
The researchers injected mice with colon cancer cells to mimic one of several types of digestive-system cancers strongly associated with the development of cachexia. Less than two weeks after the cancer started to grow, these insulin-resistant mice had become. 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 tissues, where it is used for energy.
Just three days later, the mice with cancer weight on average 20 percent less than control mice without tumors, weight loss of at least 5 percent is considered a sign of cachexia in humans. By day 19, the total weight of muscle in mice with cancer decreased by 29 percent and the weight of fat tissue was reduced by 73 percent. This rapid loss of muscle and fat suggests that these mice had actually developed cachexia.
“These data provide evidence that tumors in mice with colon cancer, insulin resistance may be involved in the development of cachexia rather than occurring as a result of cachexia,” Belury said. “And the key here is that people and animals with cachexia not want to lose weight. You can eat more and not care. There is something inside that drives this loss of fat and muscle.”
In the second study, scientists tested whether rosiglitazone can “rescue” the insulin resistance in mice with colon cancer.
In this study, mice were fed a high fat diet and randomly assigned to three groups of mice with tumors and without receiving a saline control, and in mice with tumors treated with daily injections of rosiglitazone.
Within eight days, the mice with cancer receiving rosiglitazone showed more sensitivity to insulin than did the mice with tumors that received no medication. The insulin sensitivity of mice medicated equals that of mice without tumors.
Similarly, mice that received rosiglitazone actually gained weight in this study, as mice without tumors. Mice with tumors that did not receive treatment lose fat, suggesting they were experiencing the onset of cachexia – despite high-fat diet they were eating.
In addition to halting the loss of fat and muscle, rosiglitazone reduced drastically also two biomarkers present when proteins break down, especially in muscles, and a marker indicating that the cells third is eating their own amino acids in a bid to survive .
“We found that markers of protein and muscle breakdown is greater in mice with cachexia, and then when we gave them rosiglitazone, which significantly decreased the degradation,” Belury said.
It is too soon to know whether the same drug have the same effect in humans with cancer, Belury said. Not all people with cancer develop cachexia, and it is difficult to catch before wasting and severe weight loss has occurred. And by the time the muscles begin to break down, the body reacts to the release of amino acids, ie, treatment at that time would have to take into account these reactions.
“For this research, we wanted to take cachexia, and he was having an influence on the loss of muscle mass without losing muscle has an influence back in cachexia,” Belury said.
In future studies, the scientists plan to further test the timing and dose of rosiglitazone and other insulin sensitizers to see if the experiments produce an “important universal effect,” said Belury.
Source: The Ohio State University (web)
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