NO INSULIN injections, no avoiding sugar. A daily drug can reverse diabetes in mice, opening up the possibility of an easier way for diabetics to keep their blood sugar level within safe limits.
In 2016, the number of people living with diabetes in the UK surpassed 4 million – an increase of 65 per cent over the course of a decade. Some 3.5 million have been diagnosed, but 550,000 are thought to have undiagnosed type 2 diabetes, which is linked to being overweight, and can develop later in life.
Many people develop type 2 diabetes as they age, because their body’s response to insulin – a hormone that controls how much sugar circulates in our blood – gets weaker. Some people can manage their symptoms by sticking to a restrictive diet, or using drugs to remove sugar from their system, but many of these have side effects, such as weight gain.
Such drugs manage the disease, but can’t reverse it. “We don’t have anything that can overcome insulin resistance,” says Emily Burns of charity Diabetes UK.
As a result, many people end up having to inject insulin. But a drug that restores the body’s sensitivity to insulin could change that.
Stephanie Stanford at the University of California, San Diego, and her team have developed an oral drug that can restore the ability of diabetic mice to control their blood sugar levels (Nature Chemical Biology).
“Finding a way to make cells respond to insulin again is an important and exciting strategy”
“This could lead to a new therapeutic strategy for treating type 2 diabetes,” says Stanford, whose team believes the drug could mean that fewer people become dependent on insulin injections.
“If this new drug works as described, it could be used to reverse insulin resistance, but we need to know first if it does that safely in people,” says Burns.
The drug works by inhibiting an enzyme called low molecular weight protein tyrosine phosphatase (LMPTP), which seems to contribute to cells losing their sensitivity to insulin. By hindering LMPTP, the drug reawakens insulin receptors on the surface of cells – especially in the liver – which normally absorb excess sugar from the blood when they detect insulin.
“Our inhibitor increased activation of the insulin receptor in the liver, and reversed diabetes without any apparent negative side effects,” says Stanford.
Targeting enzymes like LMPTP has long been a goal for diabetes researchers, says Daniel Drucker of the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada. So far, most of these efforts have focused on another tyrosine phosphatase enzyme, but it has proven difficult to block this without also causing side effects, says Drucker.
“Our compound is very specific for the target, but the next step is to rigorously establish if it’s safe for use in clinical trials,” says Stanford.
“Finding a way to make cells respond to insulin again is an important and exciting strategy,” says Burns. “So far, the drug has only been tested in mice, and while some research in human genetics suggests this approach could work in people too, we need more research before we know how relevant this could be for people with type 2 diabetes.”