A new molecular mechanism underlying a rare and severe form of diabetes in children has been identified by University of Iowa researchers.
The new mechanism involves a protein called ankyrin and appears to regulate specialized pancreatic cells and insulin secretionThe researchers hope that the new discovery may help identify new molecular targets for treating both rare and common forms of diabetes and hyperinsulinemia.
During the study, the team used animal and cellular models to focus on a gene mutation linked with permanent neonatal diabetes mellitus.
Children with this genetic form of diabetes have symptoms by age 6 months and require lifelong dependence on insulin to maintain proper glucose levels.
They found that the specific human gene mutation disrupts the ability of the protein ankyrin to regulate a key protein complex known as the KATP channel.
"We have known for some time that human mutations in the KATP channel complex may cause diabetes or hyperinsulinemia," said Faith Kline, Ph.D., the study's lead author and postdoctoral fellow in internal medicine in the University of Iowa Carver College of Medicine. Now we know something about how this specific KATP channel mutation results in disease.
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According to the researchers, a key finding in this study was identifying the ankyrin protein in the pancreatic beta cell, which is a type of excitable cell.
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The team found that the gene mutation prevents most KATP channels from binding with ankyrin, which typically acts as a cellular chaperone. This failure prevents the KATP channels from reaching their normal destination in the cell membrane.
The team also found that the few mutant KATP channels that do reach the pancreatic cell membrane do not respond to alterations in cellular metabolism. As a result, the pancreatic beta cells do not release insulin appropriately.
The study appears in Proceedings of the National Academy of Sciences.
Source-ANI
RAS