Genetic mutation may lead to excess insulin, even if patient has not eaten any carbs
Researchers have discovered how a genetic mutation may lead to excess production of insulin, a condition known as congenital hyperinsulinism, even if the patients have not eaten any carbohydrates.health Updated: Sep 18, 2017 15:04 IST
Researchers have discovered how a genetic mutation may lead to excess production of insulin, a condition known as congenital hyperinsulinism, even if the patients have not eaten any carbohydrates.
Since the function of insulin is to metabolise sugars, excess production of insulin leads to chronic hypoglycaemia. The brain, which devours vast quantities of energy, is perpetually undernourished. The disorder can therefore lead to serious brain damage and even death in the worst cases.
In a study published in the journal Human Molecular Genetics, the researchers described the effects of a genetic mutation in cases of congenital hyperinsulinism. Congenital hyperinsulinism starts exerting its effects from birth. Although it is considered to be a rare disease, affecting roughly one in every 50,000 newborn babies, it may be underdiagnosed.
“Unless you are looking for it, hypoglycaemia can easily go unnoticed in an infant,” said lead author of the study Pierre Maechler, a researcher at the University of Geneva (UNIGE), Switzerland. “Without intervention it can rapidly take a dramatic course,” Maechler said.
The researchers focused on a genetic mutation known to be associated with hyperinsulinism. This gene produces a protein known as GDH, which instructs the pancreas to release insulin. It normally behaves differently once the level of blood glucose passes a certain threshold.
Then GDH opens up to receive a molecule known as an accelerator that binds to it. In this way the protein moves into the active phase, which in turn sends a signal to the pancreas, causing it to produce more insulin. In congenital hyperinsulinism, the mutant gene causes the structure of the protein to change, the study said.
The protein remains permanently receptive to the accelerator molecule, whatever the level of glucose in the blood. As a result, it constantly sends signals to the pancreas, telling it to release insulin, which it then does excessively.
Insulin promotes the transfer of glucose to the muscles. If there is a constant surplus of insulin, it leads to undernourishment of the brain, which in turn results in brain damage and intellectual retardation, and to coma and even death in the most critical cases. This discovery could pave the way for new therapies for the condition for which currently available are problematic. These treatments range from almost total removal of the pancreas, which produces diabetes artificially, to administration of drugs which regulate the activity of the pancreatic cells more or less precisely but have major side effects.
“We can imagine developing a drug that inhibits the GDH accelerator by occupying the same site, which would reduce the production of insulin,” Maechler said.
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