Study Identifies Potential Mechanism Behind Inverse Relationship Between Migraines, Risk of Type 2 Diabetes

Peptides that cause migraine pain can influence insulin production in mice, possibly by regulating the amount of secreted insulin or by increasing the number of pancreatic cells that produce it, according to a study presented at the American Chemical Society’s Fall 2021 meeting. This potentially explains the mechanics behind why those who get migraines are less likely to develop type 2 diabetes, which could improve methods for the treatment or prevention of diabetes, according to the investigators.

Researchers have previously identified 2 peptides in the nervous system as playing a major role in causing the pain in migraines: calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Both of these peptides, along with the related peptide amylin, are found in the pancreas as well, where they influence the release of insulin from beta cells.

According to the investigators, because CGRP and PACAP play a role in both diabetes and migraines, they offer a potential treatment target in therapies for either condition. Migraine drugs that interfere with CGRP and its cellular receptors have recently gone on the market, and other treatments are currently in development. The current study was designed with the intention of clarifying the impact of these peptides on insulin production.

The investigators developed a technique for gathering data from just a few hundred beta cells in order to understand and analyze the activity of the peptides in mice. This technique demonstrated that CGRP lowered levels of mouse insulin 2, the analog of human insulin, according to the results of the study. The investigators said that this could counter the insulin resistance that develops in type 2 diabetes.

Diabetes is also associated with an aggregation of amylin, which may contribute to the beta cell damage that helps cause type 2 diabetes. According to the investigators, because amylin and insulin are co-secreted by beta cells, CGRP could be used to limit insulin production, and by extension limit amylin production, which could protect the cells and help to normalize their function.

PACAP is also thought to play a role in protecting against type 2 diabetes. According to the investigators, this is confusing, because PACAP has been shown to stimulate insulin release, which leads to insulin resistance. However, there is preliminary evidence that PACAP regulates insulin in a glucose-dependent manner and promotes the development of beta cells, as opposed to causing existing beta cells to work harder. The investigators are currently developing analytical methods for testing 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,” said Thanh Do, PhD, in a press release. “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.”

Because these 2 peptides are seemingly capable of protecting individuals from developing diabetes, the investigators worry that the anti-CGRP and anti-PACAP treatments currently being developed or marketed for migraine treatment could have potential consequences resulting in an increased risk of diabetes. These peptides also function in numerous other beneficial manners throughout the body, and the investigators are currently exploring other potential risks of altering their activity.

REFERENCE

How migraines protect against diabetes [news release]. EurekAlert; August 26, 2021. Accessed August 30, 2021. https://www.eurekalert.org/news-releases/924301