City of Hope (COH)

Can skeletal Muscle-Specific DOC2B Enrichment Reverse Prediabetes

Research Area

Grant Type



Peripheral insulin resistance, especially in skeletal muscle, is the major cause of prediabetes and ultimately leads to the onset of T2D. In prediabetes, exocytosis of GLUT4-containing vesicles to the cell surface is impaired, leading to insufficient glucose uptake. We have shown the double C2-like domain-containing protein beta (DOC2B) plays a key positive regulatory role in insulin-stimulated GLUT4 vesicle exocytosis and glucose uptake in skeletal muscle. Our data suggest pursuing ways to enrich DOC2B, a potential therapeutic target, will provide for early intervention for prediabetes, and for restoration of insulin sensitivity. Thus, I hypothesize that skeletal muscle-specific DOC2B plays an essential role in insulin-stimulated glucose uptake and enriching DOC2B in cells can improve skeletal muscle function to reverse prediabetes and T2D. The objective of this project is to determine the underlying mechanisms by which skeletal muscle-specific DOC2B enhances metabolic function during insulin resistance and prediabetes. I expect the identified DOC2B-mediated mechanisms will provide ways to combat impaired glucose uptake, and thus, promising results will have a positive impact on the development of new therapeutic strategies to reverse or cure prediabetes and T2D in the future.