How insulin, zinc and pH can 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 difficulty using sugar for fuel, leading to a buildup of sugar in the blood and chronic health problems.

New research led by Ayyalusamy Ramamoorthy, a professor in the FAMU-FSU College of Engineering and the National High Magnetic Field Laboratory at Florida State University, shows how zinc, pH levels and insulin work together to inhibit the buildup of protein aggregates that contribute to the disease. The work, which offers promising avenues for innovative treatments, was published in Biology of communications.

The research focuses on the complex dance between insulin and the hormone amylin, or human islet amyloid polypeptide (hiAPP). Amylin is a naturally occurring peptide hormone that plays a role in regulating blood sugar and energy balance. But human amylin can form amyloid fibers, which can destroy insulin-producing cells in the pancreas.

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

This study is notable for its innovative approach to boosting insulin’s protective capabilities against the harmful effects of IAPP. As research progresses, new treatments for the millions of people living with type 2 diabetes are closer.

“Amylin is produced in the pancreas along with insulin and tends to clump together into aggregates called amyloids,” says Sam McCalpin, a postdoctoral researcher in the Ramamoorthy lab at the National High Magnetic Field Laboratory. “They’re similar to the plaques that form in the brain in Alzheimer’s or Parkinson’s disease.”

Researchers are interested in developing drugs to break them down or prevent them from forming. In people with type 2 diabetes, amylin tends to clump together into harmful amyloid plaques, devastating the islet cells responsible for producing hormones. However, insulin is emerging as a potential hero, showing some ability to hinder amylin aggregation.

This study uncovers the nuances of their interaction, as well as the roles of zinc and pH levels, bringing scientists closer to decoding the cellular intricacies of diabetes.

“There is some evidence that insulin can help, but it is not effective enough to directly address type 2 diabetes,” McCalpin said. “So we want to use insulin as a model to design more effective treatments in the future.”

The findings promise not only groundbreaking discoveries about this biomedical mystery, but also practical solutions. The research will contribute to the development of drugs to counteract amylin toxicity, Ramamoorthy said. This could potentially revolutionize therapeutic approaches, offering hope to those battling this pervasive disease.

Co-authors of this research were Bernd Reif of the Technical University of Munich, Madalena Ivanova of the University of Michigan and Lucie Khemtemourian of the University of Bordeaux.