09:58pm Tuesday 02 June 2020

Intracellular Protein May Impact Efficacy of Common Diabetes Drug

CINCINNATI—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 three 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 co-author 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 anti-diabetic 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.”

Additional co-authors on the research study from Fan’s laboratory include: Yutian Li and Kobina Essandoh, two PhD students; Xiaohong Wang, research scientist; Xingjiang Mu and Haitao Gu, two post-doc fellows; and Shan Deng, visiting scholar, in the Department of Pharmacology and Systems Physiology. Contributing authors from Perez-Tilve’s laboratory include: Jenna Holland, senior research assistant, and Emily Yates, principal research assistant in the Department of Internal Medicine.

Other co-authors also from UC are Robert McNamara, PhD, professor in Department of Psychiatry and Behavioral Neuroscience; Anil Jegga, research associate professor in the Department of Pediatrics; and Takahisa Nakamura, assistant professor in the Department of Pediatrics.

Kai Huang, professor at the Huazhong University of Science and Technology, along with Jing Chen, research fellow at Cincinnati Children’s Hospital, Boyu Wang of Samaritan Medical Center in Watertown, NY, Tianqing Peng of Lawson Health Research Institute in London, UK and Tiemin Liu, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University in Shanghai, China, were also co-authors.

The research study received funding from the University of Cincinnati, an American Heart Association Established Investigator Award (17EIA33400063) and the National Institutes of Health grants HL-087861 and GM-112930.


 University of Cincinnati



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