Gene Therapy for Type 2 Diabetes Improves Insulin Sensitivity in Mice

One infusion improved blood sugar levels for seven weeks.



Gene therapy treatment for diabetes often focuses on Type 1 diabetes, but there now has been some reported success in using this therapy to treat Type 2 diabetes.

With gene therapy, doctors insert lab-designed genes into patients to help treat medical conditions. A research article appearing in the Journal of Clinical Investigation describes researchers using this technique to improve insulin sensitivity in laboratory mice with diabetes.

In the experiment, the mice had been given a high-fat diet to induce the type of insulin resistance that is characteristic of Type 2 diabetes. They then were given an IV infusion of a virus carrying the amino acid peptide urocortin 2. With a single treatment, the mice showed increased levels of the urocortin hormone, indicating improved insulin sensitivity; this result lasted for seven weeks. In addition, when the treatment was given to non-diabetic mice, the researchers discovered that those mice maintained fasting glucose levels that were lower than before the treatment.


The paper was authored by Renova Therapeutics co-founder Dr. H. Kirk Hammond. Dr. Hammond is a researcher and professor at the medical school of the University of California, San Diego, and a cardiologist. His lab has worked for a number of years in gene therapy for cardiovascular diseases.

For the experiment, the mice were given small incisions in the neck to expose the jugular vein, and then injected with either an infusion containing the urocortin 2/virus [UCn2/AAV8] or a saline solution. Glucose tolerance and insulin tolerance testing followed, as did blood plasma sampling. The researchers also monitored certain blood pressure and heart rate changes.


The results demonstrated that the mice given the infusion achieved glucose levels steadily below the line of what is considered hyperglycemia; this was evidence that the infusion helped prevent the onset of high blood sugar levels from a high fat diet and helped reduce high blood sugar levels that had been present before the infusion was given. Also there were indications that the infusion hastened the disposal of excess blood sugar in the mice, brought on better insulin sensitivity, and reduced the amount of fat infiltration in the liver.

In the estimation of the research team, the gene transfer approach offers an advantage over existing therapies for Type 2 diabetes in that it circumvents the need for daily oral medication or insulin therapy. In e-mail correspondence, Dr. Richard McCloskey, Renova senior clinical development officer, said the company is now developing a similar infusion to test on people who had been recently diagnosed with Type 2 diabetes. No timeline has been announced for Renova’s next round of clinical trial efforts.

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Jim Cahill is a senior writer for Insulin Nation and Type 2 Nation. Before turning to writing, he was a lawyer in government and private practice who focused on consumer protection and regulatory law. He can be contacted at jcahill@epscomm.com.