Blocking the action of a gene called Sirtuin-1 reduced the symptoms of type 2 diabetes in rats, scientists have found.
People with Type 2 diabetes suffer from high blood glucose concentrations due to insulin resistance and increased glucose production. To create a similar condition in rats, the researchers put a group of rats on a four-week diet of high-fat, fructose-rich meals.
Sirtuin-1 is a gene responsible for regulating glucose production in the liver. The researchers therefore then blocked Sirtuin-1 in the ‘diabetic’ rats by injecting them with a fragment of genetic information. This fragment – called an antisense oligonucleotide – interrupts and blocks gene expression and can be targeted to specific genes.
After Sirtuin-1 inhibition, the rats were more sensitive and responsive to insulin. The rate of glucose production fell back to normal levels, resulting in a decrease in the blood plasma. Thus the scientists believe the Sirtuin-1 gene is a cause of type 2 diabetes symptoms.
The results of this study are consistent with a recent mouse study which showed that decreased expression of Sirtuin-1 led to better insulin sensitivity. The next step is to develop inhibitors targeted to Sirtuin-1 in the liver, these will be tested in rats before moving on to primates and human clinical trials if successful.