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Scientists Find Previously Unseen Effects of Protein Buildup in Diabetic Baboons' Pancreases

Protein buildup changes the microenvironment of a key area of the pancreas, resulting in a hormone imbalance that ultimately leads to type 2 diabetes, according to a new study from The University of Texas Health Science Center at San Antonio and collaborating institutions.

Undesirable protein deposits in the islets of Langerhans, the area of the pancreas that makes glucose-controlling hormones, are increased even when blood sugar levels are barely above normal, according to a newly published study by diabetes researchers from The University of Texas Health Science Center at San Antonio.

These deposits worsen as glucose increases, which is the key finding of the study, said Franco Folli, M.D., Ph.D., associate professor of medicine at the UT Health Science Center at San Antonio. He is senior author and principal investigator of the study article published in the July 20-24 online early edition of Proceedings of the National Academy of Sciences.

The researchers examined pancreatic tissue of 150 baboons that had died of natural causes, including diabetes. The team collaborated with the Southwest Foundation for Biomedical Research in San Antonio, which has a National Primate Research Center with a nonhuman primate model of type 2 diabetes mellitus. “Diabetes researchers, including us, have shown that baboons develop type 2 diabetes and obesity as it is observed in humans,” Dr. Folli said. “These conditions are a major health concern in Texas and the U.S.”

The deposits of a protein hormone, called Islet Amyloid Polypeptide (IAPP), somehow shift the microenvironment of the islets of Langerhans, the authors noted, making it toxic to cells that produce insulin, which lowers blood glucose levels. At the same time, the microenvironment promotes the replication of cells that produce a second hormone, glucagon, which raises blood glucose levels. The cells that produce insulin are called beta cells; the cells that produce glucagon are called alpha cells.

“For reasons we don’t fully understand, beta cells die in the amyloid-altered environment, but alpha cells proliferate,” Dr. Folli said. “It’s really an imbalance. Both activities are not normal and produce an undesirable effect, ultimately type 2 diabetes.”

Scientists have long known that glucagon is increased in type 2 diabetes, but had no explanation for this phenomenon. The team’s finding of alpha cell multiplication in the damaged islets of Langerhans is therefore intriguing. “Finally we have a very plausible explanation of the increased glucagon levels,” Dr. Folli said.

The study’s first author is Rodolfo Guardado-Mendoza M.D., Ph.D., postdoctoral fellow with Dr. Folli and Ralph Defronzo, M.D., in the Health Science Center’s Department of Medicine/ Division of Diabetes. Collaborating entities included the Southwest Foundation for Biomedical Research, the Health Science Center Department of Surgery, and Mexican and Italian centers.

A grant from the National Institutes of Health was recently awarded to Dr. Folli to support this research program, in collaboration with Anthony Comuzzie, Ph.D., of the Southwest Foundation for Biomedical Research.

About the UT Health Science Center at San Antonio:

The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $668 million, the Health Science Center is the chief catalyst for the $16.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $36 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 26,400 graduates (physicians, dentists, nurses, scientists and other health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, dentistry and many other fields.

Will Sansom | Newswise Science News
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