nPOD. Beta Cell Physiology and Dysfunction

Role of myosin-I in insulin secretion

In pancreatic beta cells, insulin is produced as proinsulin and packaged into secretory granules at a region of the cell called the trans-Golgi network (TGN). After maturation which includes the conversion of proinsulin to insulin, insulin granules are trafficked to the cell membrane where their contents are released through a process known as exocytosis. Actin filaments participate in different phases of insulin granule production and release. Our laboratory studies myosin motor proteins, which associate with actin filaments and modulate their activity. We have found that loss of the unconventional myosin Myo1b reduces insulin and proinsulin content. This results in less insulin secretion from Myo1b-depletedinsulinoma cells. Importantly, using an in situ fluorescent pulse-chase strategy to track nascent proinsulin, we found that loss of Myo1b impaired the early-stage trafficking of (pro)insulin granules. Our working model is that Myo1b is involved in early-stage insulin granule formation in beta cells. As diabetes is characterized by a reduction in insulin synthesis, insulin granule formation, and insulin secretion, our goal is to determine whether Myo1b loss is associated with the impaired insulin secretion in diabetic beta cells.

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