Previously Unseen Effects Of Protein Buildup In Diabetic Baboons' Pancreases Found

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.