“Super Mice” Suggest Promising New Approach to Diabetes Medication

lab mice

Photo: Aaron Logan

Scientists at the prestigious Mayo Clinic are excited about a promising prospective treatment for type 2 diabetes. Type 2 diabetes is a result of the body losing sensitivity to insulin and no longer being able to respond to it. Current diabetes treatments concentrate on increasing insulin levels – either by administering insulin injections, or by stimulating the pancreas to produce more insulin.

A Mayo Clinic Department of Neuroscience research team, led by Malcolm Leissring, Ph.D, took a different approach – blocking the breakdown of insulin after it was released by the pancreas. Conducting studies in mice, the researchers genetically deleted an insulin-degrading enzyme, or IDE, which breaks insulin down into smaller pieces to help control insulin levels in the blood.

The IDE-less rodents were “super mice” in regards to their ability to lower their blood sugar after a meal (a problem for many diabetics). They also had higher insulin levels, weighed less, and had better overall blood sugar control.

“Insulin levels in the blood reflect the balance between how much is secreted and how fast it is broken down,” explains Leissring, “Blocking the breakdown of insulin is simply an alternative method for achieving the same goals as existing diabetes therapies.”

Unfortunately, IDE inhibitors will need some work before they can be used in humans. The “super mice” eventually overdosed on the trial diabetes drug, becoming insulin resistant and developing classic type 2 diabetes. “It’s an example of too much of a good thing becoming bad for you, explains researcher Samer Abdul-Hay, Ph.D, “Deleting all IDE is overkill”. He believes that drugs that only partially or temporarily inhibit IDE could be effective long-term diabetes medications.

The study also raises some interesting questions about how diabetes starts. Diabetes is usually believed to cause hyperinsulinemia, or excess insulin levels in the blood.  But as the “super mice” with IDE-elevated insulin levels aged, it worked the other way around – the mice lost insulin receptors, became insulin resistant, and developed type 2 diabetes.

Dr. Leissring and his team are currently working on developing more IDE inhibitors, stressing that they in the “early, but exciting days” of their research, and are still unsure if the results will apply to humans. The American Diabetes Association recently awarded them a five-year development grant – a solid indication of its interest in and support for this new avenue of diabetes research.