Scientists in Japan and the US have uncovered a molecular mechanism that links diet and ‘Type 2’ diabetes. The work opens the way to new treatments for the condition.

There is a widely accepted connection between high fat diets, obesity and susceptibility to Type 2 (adult onset) diabetes. Until now, however, the underlying causes were poorly understood, particularly at the molecular level.

Diabetes is characterised by a drop in the effectiveness of the hormone insulin. In a healthy person, a high level of glucose sugar in the blood triggers the pancreas to secrete insulin which helps the body get rid of the excess. A rise in glucose is detected by the beta cells of the pancreas, when large amounts of glucose are delivered to them by specialised transporter proteins.

High-fat diets and Type 2 diabetes go hand in hand

High-fat diets and Type 2 diabetes go hand in hand

Without these transporter proteins, the beta cells are unable to detect high glucose levels and do not secrete insulin. But what causes a deficiency in transporter proteins?

Genetically engineered mice that do not produce GnT-4a, an enzyme which helps these proteins connect with the beta cell surfaces, develop diabetes. In earlier work, Kazuaki Ohtsubo from the RIKEN Advanced Science Institute in Japan showed that a high-fat diet can cause a deficiency of this enzyme.

To investigate these earlier findings in detail, Ohtsubo and his colleagues from the University of California, USA, investigated the sequence of molecular events in pancreatic beta cells from mice and humans.

They found that high levels of fatty acids caused both transporter proteins and the GnT-4a enzyme to be produced in much smaller quantities than usual. The resulting deficiencies led to many of the symptoms associated with diabetes.

Although the underlying causes of this link are still unknown, the team hopes this knowledge could lead to the development of new treatments. “We are already searching for small chemical compounds which activate the expression of GnT-4a in pancreatic beta cells under high fatty acid conditions,” says Ohtsubo.

“These compounds could improve beta cell function and should be good candidates for new types of drugs for diabetes.”

For further information contact:

Dr Kazuaki Ohtsubo
RIKEN Advanced Science Institute, Japan
Email: gro-pr@riken.jp