Diabetes results from failure of beta (β) cells in pancreatic islets to release sufficient insulin to regulate blood sugar in the body. Researchers at Joslin Diabetes Center revealed that the chronically high sugar levels that occur early during the development of diabetes further undermine the ability of beta cells to produce insulin by reducing translation of specific mRNAs that contain the cell’s genetic instructions for making and secreting insulin. Blocking this response to high sugar levels could be a new way to prevent progression of early diabetes or even an effective strategy to improve the function of beta cells implanted in patients to cure diabetes.
The team looked at the impact of sustained elevated glucose levels on β cell mRNA translation across the entire genome using high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells, and then verified specific changes in human islets. They demonstrated that sustained high glucose selectively impairs translation of genes that serve critical roles at almost every step of glucose metabolism–coupled insulin secretion in pancreatic β cells.
