Mouse, tissue tests confirm a new pathway for insulin resistance in diabetes

Investigators at the Perelman School of Medicine at the University of Pennsylvania say they have a fresh set of animal and tissue sample tests that confirmed a new pathway for treating the insulin resistance that afflicts many diabetics.

In insulin resistance, the body produces insulin but still can't effectively process glucose. For a large number of people who develop Type 2 diabetes, the condition is triggered by an excess of fat in skeletal muscle. And the researchers were intrigued by the connection of insulin resistance with an elevation of branched-chain amino acids.

The team at Penn took that as their target and found that the amino acids created a compound called 3-HIB. That compound, they found, helps transport fat into skeletal muscle. And when you block it, you also reduce the amount of fat that gets into the muscle. Theoretically, that should make it an excellent target for developers looking to develop new meds that could be used to prevent diabetes.

"In this study we showed a new mechanism to explain how 3-HIB, by regulating the transport of fatty acids in and out of muscle, links the breakdown of branched-chain amino acids with fatty acid accumulation, showing how increased amino acid flux can cause diabetes," said project leader Zoltan Arany, an associate professor of cardiovascular medicine.

The next step, he adds, should be further studies that explore the role of 3-HIB.

"The discovery of this novel pathway--the way the body breaks down these amino acids that drives more fat into the muscles--opens new avenues for future research on insulin resistance, and introduces a conceptually entirely new way to target treatment for diabetes," Arany said.

Additional Penn authors on the study include Cholsoon Jang, Shogo Wada, Atsushi Hoshino, Boa Kim, Ayon Ibrahi, Qingwei Chu, Saikumari Krishnaiah, Aalim Weljie, and Joseph Baur.

- here's the release
- read the journal abstract

Read more on