Diabetes and Cancer: What's the Connection?
Certain cancers, such as breast, pancreatic, and colon cancer have often been associated with particular metabolic diseases, of which diabetes is the most familiar example. While the link between diabetes and cancer is well documented, a basic understanding of diabetes demonstrates why the reasoning behind it seems so paradoxical.
Very briefly, insulin serves as a “key” that opens a cellular “door,” allowing glucose to move from the bloodstream into a particular cell. Normally, our pancreas produces insulin in response to increase in blood glucose (say, after we eat a bigger dinner). The glucose travels throughout the body via the blood and insulin allows it to enter cells, where the sugar serves as fuel for a whole host of metabolic processes.
In type 2 diabetes, the primary problem concerns the inability of the body cells that receive glucose to respond to insulin. This phenomenon, called insulin resistance, results from the lifestyle that often leads to the development of type 2 diabetes: poor diet and sedentary lifestyle. Essentially, cells are over-stimulated with toxic levels of insulin from the pancreas, and they decrease the amount of the insulin receptors on their surface to prevent harm to themselves. At this point, excess glucose begins to build up in bloodstream, and individuals need to take supplementary insulin to continue being able to “unlock” their cells.
Cells need glucose to thrive and proliferate, and the link between diabetes – which starves cells of glucose – and various cancers raised one very important question: How do cells that are robbed of the essential fuel they need to grow end up growing faster than normal? Dr. Cagan and his team at the Icahn School of Medicine at Mount Sinai set out to find an answer.
Using Drosophila flies – the insect equivalent to laboratory mice – Dr. Cagan first promoted expression of two oncogenes, which caused small, malignant tumors to grow inside of the flies. He then fed the flies a diet high in sugar, leading to insulin resistance, everywhere except the tumor cells. In fact, the tumor cells experienced an increased sensitivity to insulin. Combined with the larger-than-normal concentration of glucose in the blood, from the general insulin resistance provoked by the high-sugar diet (in humans, this would be the type 2 diabetes), tumor cells were primed for aggressive growth.
The research team treated the flies with three different medications. Acarbose, specifically used to treat diabetes, blocks conversion of dietary sugar into glucose, decreasing the latter’s concentration in the blood. A drug called AD81 then turns off the two oncogenes and causes malignant cell death. The last medicine, pyrvinium, inhibits the particular signaling pathway that results in the production of insulin receptors that causes the increased insulin sensitivity. This combination of drugs severely inhibited tumor growth and progression.
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