Background: Tomosyn-2 is an inhibitor of insulin secretion. Results: Glucose induces phosphorylation, ubiquitination, and degradation of tomosyn-2. Hrd-1 is an E3-ligase responsible for tomosyn-2 degradation. Conclusion: We identified a novel mechanism whereby pancreatic -cells degrade an inhibitor of insulin secretion. Significance: Inability of -cells to degrade tomosyn-2 upon activation will lead to reduced insulin secretion and contribute to the pathogenesis of type 2 diabetes.
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