JDRF Research
Insulin-Making Protein Identified In Beta Cells
JDRF-funded researchers at the University of Massachusetts have identified a protein in beta cells that regulates the production of insulin. The finding suggests that a drug or therapy that increases the activity of this protein could enable people with diabetes to boost their own insulin production and better manage type 1 diabetes.
The protein, IRE1, operates in beta cells within the endoplasmic reticulum (ER), a large, intracellular membrane folded over many times on itself. Most proteins are assembled inside the ER before being transported to other sites within the cell to perform specific tasks. IRE1 helps regulate the process by which the insulin protein is folded into final form so it can function properly.
“We’re excited by the therapeutic applications of this finding, which could potentially benefit beta cell regeneration and islet transplantation,” said Richard Insel, M.D., JDRF’s Executive Vice President for Research.
The finding was made by Fumihiko Urano, M.D., Ph.D., and colleagues at the University of Massachusetts Medical School. It is published in the journal Cell Metabolism.
Previous JDRF-funded research led by Dr. Urano found that IRE1 has an essential role in removing abnormal proteins that accumulate in cells as the result of physiological stress, such as high blood glucose. This latest discovery suggests that a drug targeting IRE1 could potentially enhance insulin secretion and protect beta cells.
The researchers dosed mouse islets for short periods with varying concentrations of glucose and measured IRE1 activity in the beta cells. They found that higher glucose concentrations caused higher IRE1 activity, suggesting IRE1’s role in secreting insulin in response to hyperglycemia.
When the researchers blocked IRE1’s signals, the production of insulin decreased, further establishing the link. The study shows that IRE1 is activated by short-term increases in glucose levels, allowing the body to synthesize more insulin when needed.
The researchers also found, however, that sustained periods of high glucose make IRE1 overactive. That stalls insulin production and also causes a buildup of abnormal proteins in the ER, resulting in beta cell damage.
The researchers suggest that drugs regulating IRE1 activity for short periods could enhance the body’s insulin production. This might delay the development of type 1 diabetes, or reduce the amount of external insulin needed by type 1 patients. Further animal tests will establish whether IRE1 can be activated only to the extent that it provides benefits.