A protein that might play a vital role in how the human body controls blood glucose levels has been identified by investigators at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine. According to the study published in the current issue of Pancreas, the protein named Islet Homeostasis Protein (IHoP) may represent a new target for treating people with type 1 diabetes.

Bryon E. Petersen, Ph.D., professor of regenerative medicine and senior author, explained:

“This data may change the current thinking about what causes
type 1 diabetes.

Much more research is needed to understand exactly how the protein functions, but its discovery opens a new door to better understand and hopefully develop new treatments for this currently incurable disease.”

So far, IHoP has been confined in the pancreas of both rodents as well as humans. The protein is located in the pancreatic islets, a collection of cells that excrete the hormones glucagon and insulin that collaborate in order to control blood glucose.

Glucagon increases blood glucose levels in healthy people, while insulin helps decrease sugar levels by transferring blood glucose into the body’s cells.

In individuals with type 1 diabetes, blood glucose levels are too high, as the pancreas produces insufficient insulin needed to lower sugar levels. Type 1 diabetes affects approximately 5% of individuals with diabetes.

According to the team, IHoP is located inside the glucagon-producing cells of the islets. High levels of the protein were detected in both humans and mice without diabetes. However, there was no expression of IHoP after the development of diabetes, indicating that IHoP might play a role in controlling blood glucose levels by regulating the balance between glucagon and insulin.

Rodents lost glucagon expression after the investigators prevented production of IHoP. This resulted in a series of events that caused insulin levels to decrease and glucagon levels to increase as well as death of insulin-producing cells.

Lead researcher Seh-Hoon Oh, Ph.D., and instructor of regenerative medicine at Wake Forest Baptist, explained:

“In a nutshell, IHoP appears to keep blood sugar regulation in check. When IHoP isn’t present, it throws the pancreas into a critical state and starts the process that results in type 1 diabetes.”

Type 1 diabetes is currently believed to be caused by a viral or environmental trigger in genetically susceptible individuals that causes white cells in the body to fight against insulin producing cells. These cells are completely destroyed within 10 to 15 years after diagnosis.

This study backs the theory that cell death plays a part in the development of type 1 diabetes, although results indicate that IHoP might influence the process. The teams’ next steps will be to investigate how the protein regulates the interaction of glucagon and insulin.

The National Institutes of Health funded the study. Co-investigators are Houda Darwiche, Ph.D., Santa Fe College, Gainsville, Fla., Jae-Hyoung Cho, M.D., The Catholic University of Korea, Seoul, South Korea; and Thomas Shupe, Ph.D., Wake Forest Baptist.

Written by Grace Rattue