How insulin, zinc, and pH block harmful protein clumps linked to type 2 diabetes

An estimated 462 million people worldwide have type 2 diabetes, a chronic disease in which the body has trouble using sugar for fuel, causing sugar to build up in the blood and lead to chronic health problems.

New research led by Ayyarsamy Ramamoorthy, professor at the FAMU-FSU College of Engineering and the Florida State University-based National High Magnetic Field Institute, shows how zinc, pH levels and insulin work together to inhibit the buildup of protein clumps that cause the disease. The research points to a promising path toward innovative treatments. Published in Communication Biology.

This study focuses on the complex relationship between insulin and the hormone amylin, namely human islet amyloid polypeptide (hiAPP). Amylin is a naturally occurring peptide hormone that plays a role in regulating blood glucose levels and energy balance. However, human amylin can form amyloid fibrils, which can destroy insulin-producing cells in the pancreas.

“The core of our research is understanding the complex effects that insulin has on amylin aggregation and resulting toxicity,” said Ramamoorthy, who led the study. “These are crucial factors in understanding the pathophysiology of type 2 diabetes.”

What makes this study stand out is its innovative perspective of enhancing insulin's protective ability against the harmful effects of IAPP. As research progresses, new treatments for the millions of people suffering from type 2 diabetes are closer to becoming a reality.

“Amylin is produced in the pancreas along with insulin and has a tendency to clump together into aggregates called amyloid,” says Sam McAlpin, a postdoctoral researcher in Ramamoorthy's lab at the National High Magnetic Field Laboratory. “Amyloid is like the plaques that form in the brain in Alzheimer's and Parkinson's diseases.”

Researchers are interested in developing drugs that could break down amylin or stop it from forming. In people with type 2 diabetes, amylin tends to clump into harmful amyloid plaques that destroy the hormone-producing pancreatic islet cells. But insulin has shown the ability to stop amylin from clumping, and has emerged as a potential hero.

The study unravels the nuances of those interactions, along with the roles of zinc and pH levels, bringing scientists one step closer to unraveling the cellular complexities of diabetes.

“There's evidence that insulin helps, but it's not strong enough to have a direct effect on type 2 diabetes,” McAlpin said, “so we want to use insulin as a model to develop more effective treatments in the future.”

The findings promise not only groundbreaking insights into this biomedical mystery, but also practical solutions: Ramamoorthy said the research will aid in the development of medicines aimed at neutralizing amylin's toxicity, which could revolutionize treatment approaches and offer hope to those battling this widespread disease.

Co-authors of the study are Bernd Reif of the Technical University of Munich, Madalena Ivanova of the University of Michigan and Lucy Kemtemlian of the University of Bordeaux.