“We believe that the findings from this study can serve as a platform to design new medications to treat diabetes or its complications,” said Bernal-Mizrachi, Chief of the Division of Endocrinology, Diabetes and Metabolism in the Department of Medicine and Deputy Director of Beta Cell Biology and Signal Transduction at the Diabetes Research Institute at the University of Miami Miller School of Medicine.
Bernal-Mizrachi has focused his research on understanding the molecular mechanisms that govern the growth and survival of islet beta cells, which store and release insulin, a hormone that affects the concentration of glucose (a form of sugar) in the blood. That includes examining the insulin-signaling pathway in the regulation of beta cells (β cells).
“Type 2 diabetes occurs when insulin-producing cells fail to adequately adapt to the increased insulin demand in obesity,” said Bernal-Mizrachi. How insulin-producing cells fail remains controversial, but exposure to chronic high glucose — as well as stress on the endoplasmic reticulum (ER), which manages proteins within cells — have been implicated, Bernal-Mizrachi said. “This study has shown that mice lacking OGT in their beta cells develop diabetes and experience beta cell failure because of increased stress on the ER.”
Building on that research, Bernal-Mizrachi’s group has shown that OGT helps regulate glucose levels in part by controlling ER stress responses in the cell and promoting beta cell survival through the kinase Akt signaling pathway. He was lead author of the recent study, “Disruption of O-linked N-Acetylglucosamine Signaling Induces ER Stress and Cell Failure,” with co-authors from the University of Michigan and the University of Minnesota.
“Given the importance of ER stress and Akt signals in the development of type 2 diabetes, these findings place OGT as a major regulator of glucose levels,” Bernal-Mizrachi said. “Our study also provides new insights into the toxic damage to the beta cells caused by chronic hyperglycemia or high blood sugar.”
Bernal-Mizrachi is an elected member of the American Society for Clinical Investigation. He serves on the editorial board of leading journals in the field of endocrinology, including American Journal of Physiology – Endocrinology and Metabolism and Molecular Endocrinology. He also serves as an associate editor for Islets and Clinical Diabetes and Endocrinology.
Bernal-Mizrachi’s clinical interests are in the areas of diabetes management, and he sees patients in UHealth’s ambulatory care centers in addition to his active research program.
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