Wayne State University

$2.58 million NIH grant to Wayne State aims to improve type 2 diabetes treatment

DETROIT – Zhengping Yi, Ph.D., professor of pharmaceutical sciences in the Eugene Applebaum College of Pharmacy and Health Sciences and director of the Proteomics Research Laboratory at Wayne State University, is leading a research team that was awarded more than $2.5 million from the National Institute of Diabetes and Digestive Kidney Diseases of the National Institutes of Health. The team will work to discover the abnormality in protein phosphatase 1 that contributes to the development of insulin resistance and type 2 diabetes.

Type 2 diabetes has become a national and global epidemic. More than 26 million American adults have type 2 diabetes. According to the Centers for Disease Control and Prevention, the U.S. diabetes prevalence may increase to 30 percent by 2050.

Insulin, a hormone made in the pancreas, helps cells absorb glucose and convert it into energy. Insulin resistance is a condition in which the body produces insulin, but the insulin sensitive tissues (e.g., skeletal muscle) do not use it effectively. Excess glucose builds up in the bloodstream, leading to type 2 diabetes and other serious health disorders such as cardiovascular disease and chronic kidney disease. Obesity and lack of physical activity contribute to the problem; however, the exact causes of insulin resistance are not completely understood.

Most research related to insulin resistance and type 2 diabetes focuses on kinases, a group of enzymes that change the function and activity of proteins by adding phosphate groups to them. Yi and his team are taking a different approach by studying another group of enzymes called phosphatases that do the exact oppositethey regulate activity of proteins by removing phosphate groups from them. It is known that protein phosphatase 1 regulatory subunit 12 (PPP1R12) controls the activity of protein phosphatase 1, one of the major phosphatases. Nonetheless, little is known about how PPP1R12 contributes to skeletal muscle insulin resistance and type 2 diabetes.

“We suspect that there are lower amounts of PPP1R12 and abnormal interactions involving PPP1R12 in skeletal muscle of obese, non-diabetic individuals and obese type 2 diabetes patients as compared to healthy, lean individuals,” said Yi. “We believe lower levels of PPP1R12 contribute to the development of insulin resistance and type 2 diabetes. We plan to test this hypothesis by using a combination of clinical studies, in vitro cell studies and cutting-edge proteomics studies to measure the physiological processes associated with these conditions, identify possible causes and analyze how cells react to their environment.”

The five-year grant for the study, “Serine/Threonine Protein Phosphatase 1 in Insulin Resistance and Type 2 Diabetes,” began Sept. 25, 2015, and provides researchers with the support needed to extend and confirm their preliminary discoveries. Led by Yi, the principal investigator, the team also includes Wayne State co-investigators Anjan Kowluru, Ph.D., professor of pharmaceutical sciences; Assia Shisheva, Ph.D., professor of physiology; Berhane Seyoum, M.D., associate professor of medicine and interim chief of the endocrinology division; Bo Wang, Ph.D., associate professor of pediatric research; Sorin Draghici, Ph.D., professor of computer science; and Xiangmin Zhang, Ph.D., assistant professor (research) of pharmaceutical sciences, as well as University of Michigan co-investigator Jeffrey Horowitz, Ph.D., professor of  movement science.

“Our goals are to help individuals who currently have type 2 diabetes and to reverse the alarmingly rapid increase of type 2 diabetes,” said Yi. “By learning more about the impact protein phosphatase 1 has on insulin resistance in skeletal muscle, we can gain new insights about its causes and create drugs that will prevent and treat the disease more effectively.”

The grant number for this NIH award is DK107666.

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About the Eugene Applebaum College of Pharmacy and Health Sciences
The Eugene Applebaum College of Pharmacy and Health Sciences, one of the founding colleges of Wayne State University, is committed to advancing the health and well-being of society through the preparation of highly skilled health care practitioners and to conducting groundbreaking research to improve models of practice and methods of treatment in pharmacy and the health sciences. To learn more, visit cphs.wayne.edu.   

About Wayne State University 
Wayne State University is a premier urban research institution of higher education offering more than 380 academic programs through 13 schools and colleges to more than 27,000 students. For more information, visit wayne.edu