Researchers Develop New Model for the Study of Diabetic Neuropathy

Providing a clearer understanding of the role nerves play in normal pancreatic islet function, investigators at the Miller School’s Diabetes Research Institute and Department of Medicine have created a new model that demonstrates how the nervous system stimulates pancreatic islets in living organisms.

Published online December 10 in advance of print in the prestigious journal Proceedings of the National Academy of Science (PNAS), their research offers direct experimental proof of nervous system input to the islets and will facilitate the real-time study of diabetic neuropathy, or nerve damage, that occurs due to chronic high blood sugar levels in about 50 percent of people with diabetes.

“The study demonstrates unequivocally that the nervous input to the islet plays an essential role in regulating blood sugar,” said Alejandro Caicedo, Ph.D., research associate professor of medicine, and the paper’s senior author. “Although nervous input to the islet has been assumed all along, direct experimental proof has not been provided. The main reason for this is that selectively stimulating the nerves that go to the islets without simultaneously affecting other organs that possibly affect glucose metabolism had not been possible.”

For the study, “Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function,” the researchers transplanted islets into the anterior chamber of the eye of diabetic mice and then used light to manipulate the existing nerves of the iris that control the size of the pupil in response to light. The result: they were able to change the islet function and glucose metabolism, and show that existing nerves stimulated the islet grafts.

“Just as many organs of the body are regulated by the nervous system, we have now established that function of the pancreatic islets is regulated by the nervous system,” explained the study’s lead author, Rayner Rodriguez-Diaz, Ph.D., research associate at the Diabetes Research Institute (DRI).

Added Midhat Abdulreda, Ph.D., research assistant professor of surgery at the DRI, and a key contributor, “The nervous input adapts the secretion of insulin and other islet hormones to behavioral responses, ensuring that blood sugar is available as fuel for the body.”

In addition to Caicedo, Rodriguez-Diaz and Abdulreda, other researchers on the study were co-senior author Per-Olof Berggren, Ph.D., adjunct professor of surgery at the DRI; Ruth Damaris Molano, D.V.M., scientist; Alexander Formoso, B.S., lab volunteer; Itai Gans, B.S., lab volunteer; Over Cabrera, Ph.D., former postdoctoral associate; Judith Molina, Ph.D., postdoctoral associate; Alberto Fachado, Ph.D., postdoctoral associate; DRI Director Camillo Ricordi, M.D., the Stacy Joy Goodman Professor of Surgery, Distinguished Professor of Medicine, Professor of Biomedical Engineering, and Microbiology and Immunology; Antonello Pileggi, M.D., Ph.D., research associate professor; and from the Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Ingo Leibiger, Ph.D., associate professor of cell biology.

Their work was funded by the Diabetes Research Institute Foundation and grants from the National Institutes of Health, the Juvenile Diabetes Research Foundation, the European Foundation for the Study of Diabetes/Merck Sharpe and Dohme Basic Research program; the Strategic Research Program in Diabetes at Karolinska Insitutet; Skandia Insurance Company, Ltd.; Berth von Kantzow’s Foundation; the Knut and Alice Wallenberg Foundation; VIBRANT; the Swedish Research Council; Novo Nordisk Foundation; the Swedish Diabetes Association; the Family Erling–Persson Foundation; the Söderbergs Foundation; the Stichting af Jochnick Foundation; and the World Class University Program through the National Research Foundation of Korea.

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