Discussions of diabetes typically focus on insulin, which is made by the beta cells in the pancreas. Notably, the beta cells also make another hormone called amylin. Indeed, these cells secrete amylin into the bloodstream whenever they secrete insulin. The hormone has several effects. It acts on alpha cells in the pancreas to inhibit their secretion of a hormone that raises glucose levels called glucagon. It also acts on the brain to reduce appetite and increase a sense of satiety and on the stomach to slow its emptying of food into the gut. These effects help to reduce the increase of glucose levels after eating and work in concert with insulin which lowers glucose levels.
These effects of amylin have led scientists to study whether it can be given to people with diabetes to control glucose levels. But first, they had to solve a challenging problem in chemistry. When human amylin is injected into the body it has a tendency to accumulate in useless, and potentially harmful clumps called amyloid. This is related to the high concentration or amount of amylin at the site of injection, and does not occur with the low concentrations of amylin that naturally circulate in people without diabetes. A similar problem occurs when the beta cells of people with diabetes are stimulated to make and secrete insulin to lower glucose levels. The increased amylin that is made at the same time can sometimes form amyloid within the cells because of the high concentrations. This can damage the beta cells and accelerate progression of diabetes.
The tendency of amylin to form amyloid led scientists to modify the amylin molecule. The modified molecule has the effects of amylin but does not make amyloid. It is this new molecule that was tested and eventually approved to treat diabetes. Pramlintide is the most commonly used version of this modified amylin molecule.
The story of amylin is a good example of how understanding normal physiology can lead to better treatments for people with diabetes.
About the author
Eamon Fitzpatrick
Eamon is a graduate student at the University of Alberta, working as part of the Alberta Diabetes Institute. Eamon’s research is focused on how Human Islet Amyloid Polypeptide (hIAPP, a.k.a. amylin) aggregation impacts the blood vessels of the islet. He hopes to understand the cellular mechanisms of amyloid damage, so that future research can find ways to circumvent this damage and improve islet health in diabetes.
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