JDRF-funded researchers in Boston, USA, have developed a way to support insulin in removing glucose from the blood, without increasing a person’s risk of hypoglycaemia.
The chemical, known as a glucokinase activator, could also indirectly improve the survival rate of beta cells, and so could theoretically be used to treat both the causes and the symptoms of type 1 diabetes.
Glucokinase activators are so called because they support the work of molecule called glucokinase. This is produced by the body to help remove glucose from the blood, converting it into a similar chemical that can be either stored or broken down. Because of this, glucokinase activators have been investigated in people with type 2 as a complement to insulin in lowering glucose levels.
In addition, some studies have suggested that the presence of glucokinase supports healthy beta cell growth, which would be beneficial to people with type 1. This would also require a glucokinase activator, since in the body glucokinase production is encouraged by rising insulin levels – something that people with type 1 lack since they no longer produce their own insulin.
However, previous attempts at formulating glucokinase treatments have focused on changing the shape of the glucokinase molecule to make it better at interacting with glucose. This is useful when glucose levels are high, as the removal can happen more quickly, but when glucose levels fall, this increased ability to react runs the risk of causing hypoglycaemia, since unmodified glucokinase would normally stop working below a certain level.
The research team, led by Drs Loren Walensky and Nika Danial, created a new glucokinase activator that drives glucokinase to remove glucose more efficiently, but stop once levels fall to normal – at the point when it naturally stops working.
This would allow it to work without increasing the person’s risk of hypoglycaemia.
Although the research is currently at an early stage – in pre-clinical lab studies – the investigators suggest the molecule could eventually be used alongside insulin to help manage glucose levels. They predict that this will be especially useful for people with type 2, given the lower levels of glucokinase found in people with type 1, but say that ‘improvement of both beta cell function and mass through increased glucokinase activity may well expand the potential utility of synthetic glucokinase activators beyond [type 2] to restoration and maintenance of functional beta cell mass for the treatment of type 1 diabetes.’
The research was published in the journal Nature Structural & Molecular Biology.