Critical link between obesity and diabetes identified

Dr. Philip Shaul and Dr. Chieko Mineo, who lead a team that discovered a major mechanism by which obesity causes type 2 diabetes, are pictured in a lab.
Dr. Philip Shaul and Dr. Chieko Mineo lead a team that discovered a major mechanism by which obesity causes type 2 diabetes.

DALLAS – Nov. 27, 2017 – UT Southwestern researchers have identified a major mechanism by which obesity causes type 2 diabetes, which is a common complication of being overweight that afflicts more than 30 million Americans and over 400 million people worldwide. 

Researchers found that in obesity, insulin released into the blood by the pancreas is unable to pass through the cells that form the inner lining of blood vessels. As a result, insulin is not delivered to the muscles, where it usually stimulates most of the body’s glucose to be metabolized.  Blood glucose levels rise, leading to diabetes and its related cardiovascular, kidney and vision problems, said Dr. Philip Shaul, Director of the Center for Pulmonary and Vascular Biology in the Department of Pediatrics at UT Southwestern.

“It was totally unpredicted that a major problem in obesity is the delivery of circulating insulin to your muscle.  It was even more surprising that this problem involves immunoglobulins, which are the proteins that make up circulating antibodies,” said Dr. Chieko Mineo, Associate Professor of Pediatrics, who is a co-senior author on the report with Dr. Shaul.

The researchers found that obese mice have an unexpected chemical change in their immunoglobulins. “The abnormal immunoglobulins then act on cells lining blood vessels to inhibit an enzyme needed to transfer insulin from the bloodstream into the muscle,” said Dr. Shaul, who holds the Associates First Capital Corporation Distinguished Chair in Pediatrics.  “Type 2 diabetes patients have the same chemical change, and if we give a mouse immunoglobulins from a type 2 diabetic individual, the mouse becomes diabetic.”

The findings reported in The Journal of Clinical Investigation may lead to new tools for diabetes risk screening and new avenues for diabetes prevention or treatment. The researchers identified an agent that they could administer to mice that prevents the chemical change in immunoglobulins that occurs with obesity and preserves healthy glucose status.  The researchers plan to test this strategy in humans in the near future.

Funding for the study came from the American Diabetes Association, the American Heart Association, The Hartwell Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT) and the National Institutes of Health (NIH).  Further research on both adults and children is under way with support from The Hartwell Foundation and the National Institutes of Health.

Other researchers involved were Dr. Keiji Tanigaki, senior research scientist and first author; Dr. Wanpen Vongpatanasin, Director of the Hypertension Section and holder of the Norman and Audrey Kaplan Chair in Hypertension Research at UT Southwestern; Dr. Jennifer Kohler, Associate Professor of Biochemistry; Dr. William Holland, Assistant Professor of Internal Medicine in the Touchstone Diabetes Center at UT Southwestern; and collaborators from the University of Texas at Dallas, University of Alabama, University of Georgia, and Imperial College London.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.