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How too much fat damages the pancreas in Type 2 Diabetes

May 2020

Diabetes is a disease of uncontrollable high blood glucose. Insulin, the hormone that reduces blood glucose, is secreted from beta cells embedded in the pancreas in structures called islets. Although overnutrition has been blamed for the inability of beta cells to secrete enough insulin in type 2 diabetes, it has remained unclear how overnutrition causes beta cells to fail. This is a critical question to solve in order to develop effective therapy to protect beta cells in conditions of overnutrition and to cure type 2 diabetes.

The research team led by Yumi Imai, MD, Associate Professor of Internal Medicine, Endocrinology and Metabolism and Fraternal Order of Eagles Professor for Diabetes Research, has been tackling this key question using advanced techniques including gene modulation and imaging tools in islets from human organ donors, which has led to new exciting findings that will be featured in the June 2020 issue of “Diabetes”, a flagship basic research journal of the American Diabetes Association. The research team showed that an enzyme called adipose triglyceride lipase (ATGL) is a pivotal enzyme that digests lipids (fats) in human beta cells and that fatty acids released by this enzyme are critically important for the stability of a protein called syntaxin 1a that mediates the final step of insulin secretion. However, the new research showed that this process of fat digestion, called lipolysis, is impaired in human islets obtained from individuals affected by type 2 diabetes. Thus, the research unmasked a previously unrecognized pathway that may explain why beta cells fail to secrete insulin and become loaded with lipids in type 2 diabetes. While more research is needed to find a way to correct the defect in lipolysis in beta cells affected by type 2 diabetes, the study has identified a potential new target to improve insulin secretion and holds high promise to lead to new drug therapies for type 2 diabetes.