Inhibiting MondoA protein could prevent development of type 2 diabetes

US researchers have identified a potential new drug target that could prevent the development of type 2 diabetes.
Scientists at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have shown that blocking a cellular glucose sensor in muscle improves insulin resistance, which is a precursor to type 2 diabetes.
A protein called MondoA was found to play a primary role in linking insulin resistance and the accumulation of fat in muscle, and the researchers hope these findings could lead to pre-clinical trials in which drugs are tested to inhibit MondoA.
A study team led by Daniel P. Kelly, M.D., professor and director of SBP’s Centre for Metabolic Origins of Disease, wanted to investigate the accumulation of fat in muscle, which is an early marker of insulin resistance, and decreased import of glucose in the body.
Kelly and colleagues examined whether these two processes are linked, and screened thousands of molecules to assess if they increased glucose uptake in muscle cells and blocked fat synthesis.
When they investigated a molecule called SBI-477, they found that MondoA regulated genes involved in both of these actions.
“Our experiments showed that this protein regulates genes involved in synthesizing fats as well as inhibiting insulin signalling,” said Kelly.
“Until now, it wasn’t clear why people who are insulin resistant accumulate fat in their muscle. These results show that MondoA is one mechanism that ties these phenomena together, serving as a gatekeeper for fuel burning in muscle.”
Inhibiting MondoA has been shown to mitigate insulin resistance in mice fed a high-fat diet, and the researchers’ next step is to develop better molecules that prevent MondoA from working.
“Directly enhancing glucose uptake by muscle and other tissues is a very different strategy from those of other anti-diabetic drugs in development. Since this action would favour energy burning, it may also have beneficial effects on overall metabolism and body weight,” Kelly concluded.
Benedict Jephcote, Head of Education at Diabetes.co.uk, said: “While researchers are working on new drug treatments to improve the treatment of type 2 diabetes, it’s worth noting that every drug treatment developed to date has brought side effects.
“Fortunately, we have the opportunity to improve insulin sensitivity, and therefore improve type 2 diabetes management, through diet. This can reduce your dependence on medication and your exposure to side effects. For more information, visit Diabetes.co.uk’s Low Carb Program.”
The findings appear in the Journal of Clinical Investigation.