Christian Rask-Madsen, M.D., Ph.D., Studies Links Between Cancer and Diabetes
Tuesday, June 17, 2014
By some estimates, people with type 2 diabetes can have up to a 30 percent increased risk for colorectal cancer. Christian Rask-Madsen, M.D., Ph.D., Assistant Investigator in the Section on Vascular Cell Biology, and Assistant Professor at Harvard Medical School, is investigating why in a series of experiments recently funded by the National Institutes of Health (NIH).
One prevailing theory as to why this happens has to do with insulin resistance. Insulin, aside from serving as the gatekeeper for getting glucose into cells, also acts as a growth hormone. In people with insulin resistance, the body floods itself with insulin in attempts to get the glucose into cells, a situation known as hyperinsulinemia. According to this theory, the excess insulin promotes the growth of cancer cells. This idea is well supported by research, but experiments from Dr. Rask-Madsen’s lab seem to suggest there’s more at play, and the culprit is likely to turn out to be inflammation.
Dr. Rask-Madsen had shown in a previous study focused on plaque build-up in arteries that insulin resistance in cells that make up the artery lining stimulated the entrance of white blood cells into the surrounding tissue. The action of the white blood cells caused inflammation, similar to what happens in your body when it’s healing after an injury. But this inflammation was chronic, meaning it didn’t go away. White blood cells kept worming their way into the tissues, producing a constant inflammation.
“We know that chronic, low-grade inflammation promotes cancer, that’s been known for many years,” said Dr. Rask-Madsen. So he designed an experiment to see if that persistent inflammation brought on by insulin resistance would increase tumor growth.
He deleted the gene for insulin signaling in a mouse model that was already susceptible to developing tumors. In doing this, he created a model of extreme insulin resistance—so much so that there was no insulin action in the artery lining tissues whatsoever. Because no insulin was interacting with these tissues, any tumor increase would necessarily be due to the inflammation. They also kept a group of tumor-susceptible, non-insulin resistant mice as controls.
So far, the experiment shows that insulin resistance makes a difference. “[The insulin resistant] mice have more tumors than the controls,” he said. “And so this is a different way of looking at the problem. Maybe in some situations it’s not the hyperinsulinemia by itself, but it’s the insulin resistance causing something to happen in the tissue that’s surrounding the tumor cells that’s the culprit. So we’re not saying that it is the root cause of or that it initiates tumors, we’re saying that it helps tumors grow once they’re formed.”
This study is still ongoing, but Dr. Rask-Madsen is already planning the next step. He wants to see if tumor-susceptible mice with improved insulin signaling show a decrease in tumor formation as compared to controls.
If his research proves that insulin resistance is a contributor to tumor formation, it will be a further impetus for people with type 2 diabetes to take insulin sensitizers, and for pharmaceutical companies to create even better insulin analogs or other medications that improve the body’s ability to use insulin.
“It’s not enough to be content that you improve metabolism. You want to look further ahead and be sure that you prevent the later complications,” said Dr. Rask-Madsen. “If drugs that improve insulin signaling can work directly on tissue where these complications take place and have a beneficial effect that could potentially be a good thing.”
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