Migraines really suck, but to sufferers, maybe a lack of diabetes could be a consolation. A new study by the American Chemical Society has found that those who get the pleasure of getting skull-crushing headaches are also less likely to develop type 2 diabetes.
If the relationship between the two afflictions sounds odd, it’s because it kind of is.
“Migraines happen in the brain, while diabetes is associated with the pancreas, and these organs are far from each other,” says Thanh Do, Ph.D., the project’s principal investigator. His group became interested in the subject after a number of papers described an inverse relationship between the conditions.
The rapport between the two breaks down to how the peptides that cause migraine pain can also influence the production of insulin. Researchers believe the production comes down to the number of pancreatic cells which produce insulin.
The scientists already knew that two peptides in the nervous system — calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP) — played a major role in causing the pain of migraines. These same peptides, along with the related peptide amylin, can also be found in the pancreas. There, they influence the release of insulin from beta cells.
Insulin is produced by the beta cells of the pancreatic islets. It is released when you have just eaten and the level of glucose in your bloodstream is high. Insulin then stimulates the uptake of glucose into cells, lowering your blood sugar level. Your muscles and liver can use glucose either for immediate energy or to be put in storage as glycogen until it’s needed.
In type 2 diabetes, those other cells become resistant to insulin and less capable of absorbing glucose, leading to high blood sugar levels. The beta cells initially compensate by ramping up insulin production but eventually wear themselves out and die, exacerbating the issue.
Due to their role in migraine and diabetes, CGRP and PACAP both offer targets for therapies that could treat either of the two illnesses. Migraine drugs that interfere with CGRP and its cellular receptors recently went on the market and other treatments are being studied. However, more research is needed to clarify the peptides’ effects. Do and his team from the University of Tennessee are trying to clear up contradictory discoveries about the peptides’ bearing on insulin.
Do’s team devised a method to glean data from just a few hundred beta cells. Using this technique, they reported showed that CGRP lowered levels of insulin in mice. That, in turn, could counter the insulin resistance which develops in type 2 diabetes. However, CGRP was less successful when it came to lowering insulin levels in humans.
Diabetes is also associated with the aggregation of amylin. These aggregates could contribute to the beta cell damage that helps cause type 2 diabetes. Because amylin and insulin are co-secreted by beta cells, using CGRP to limit insulin production could also limit amylin production, Do says. That could protect the cells and help normalize their function.
PACAP, too, is thought to play a protective role against type 2 diabetes. That can be somewhat confusing since PACAP has also been shown to stimulate insulin release, which leads to insulin resistance.
Do’s group’s initial findings in trying to figure out the conundrum show that PACAP’s actions could depend on glucose levels. The researchers found preliminary evidence that PACAP regulates insulin in a glucose-dependent manner and promotes beta cell proliferation, rather than prodding existing beta cells to work harder — thus preventing the risk of tiring out the existing cells. They are developing analytical procedures to test this.
“Despite these positive results, you can’t inject CGRP and PACAP into the body as therapeutic strategies for diabetes because these peptides cause migraine pain,” Do says. “But once we understand how they exert their effects on insulin secretion, we can design peptide analogs that would control insulin but would not bind to the pain receptor.”
However, Do and other researchers are afraid that current migraine medications currently on the market could actually up the risk of diabetes since some are anti-CGRP and anti-PACAP treatments. In addition, these peptides are involved in numerous other beneficial functions in the body, such as blood vessel dilation. Because of this, Do and other scientists are also investigating the possible hazards of altering the peptides’ activity.
So the next time you have a headache coming on, just know that at least there is a bright side.
