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Intracellular protein may impact efficacy of common diabetes drug

University of Cincinnati Academic Health Center News Jun 21, 2018

Scientists at the University of Cincinnati (UC) College of Medicine are studying how a small intracellular protein, Hsp20, may affect the efficacy of a common drug used to treat diabetes.

The research is available online in the June 19 issue of the scholarly journal Cell Reports.

"We have investigated the functional role of Hsp20 in the heart for more than 15 years and found that this protein can provide protection against various stress condition-induced heart injuries,” says Guo-Chang Fan, PhD, associate professor in the Department of Pharmacology and Systems Physiology.

Fan says for the past 3 years he worked closely with Jiangtong Peng, PhD, a visiting scholar in his laboratory from Tongji Medical College, Huazhong University of Science and Technology in Wuhan, Hubei, China, to explore Hsp20’s possible function in fat cells. Peng is the lead author of the research study.

"We created the global knockout of Hsp20 animal models and surprisingly observed that Hsp20-null animal models develop obesity without diabetes,” says Fan, also a member of the UC Heart, Lung, and Vascular Institute.

More interestingly, Hsp20 promotes the degradation of the cellular target for thiazolidinedione (TZD), one of the most commonly prescribed drugs for diabetes, explains Diego Perez-Tilve, PhD, research assistant professor in the UC Department of Internal Medicine and a coauthor of the research study. TZD works better in Hsp20-null animal models than in control wild-type animal models by improving the effect of insulin in the cells of fat tissue.

"Eliminating Hsp20 results in an increase in the antidiabetic efficacy of TZD in animal models,” says Perez-Tilve. "Thus strategies aimed to block Hsp20 in fat cells may improve the effectiveness of TZD on diabetes.”

Diabetes is a chronic (long-lasting) disease that affects how your body turns food into energy, according to the Centers for Disease Control and Prevention (CDC). As a result of diabetes, the body either doesn’t make enough insulin, which acts like a key to let the blood sugar into your body’s cells to use as energy, or can’t use the insulin it makes as well as it should.

About 30 million American adults have diabetes, according to the CDC.

"These studies are eminently mechanistic and would require pharmacological drug development to confirm the therapeutic value of inhibiting Hsp20 for the treatment of diabetes in humans,” says Perez-Tilve. "Nonetheless, they offer a proof-of-concept on how indirectly manipulating the target of TZDs may provide benefits to improve metabolic control.”

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