Kv2.1 Clustering and Spatial Patterning of Exocytosis in Human Pancreatic β-Cells

• Author / Creator

  Fu, Jianyang

• Diabetes is a common metabolic disorder, which is characterized by peripheral insulin resistance and a relative insufficiency of insulin secretion from human pancreatic β-cells. Recent insights indicate that impaired insulin secretion is a key determining factor in type 2 diabetes mellitus (T2D). Thus, a better understanding of the mechanisms mediating granule exocytosis events underlying insulin secretion from human single β-cells is essential.
  
  This present thesis investigates an ion channel, Kv2.1, which regulates the electrical firing of isolated pancreatic β-cells from both non-diabetic and T2D donors. My studies show that expression of Kv2.1 is downregulated in T2D donors. In insulin secreting cells, including pancreatic β-cells, Kv2.1 is compartmentalized in clusters and colocalized with insulin granules. Overexpression of Kv2.1 and restoration of Kv2.1 clusters can rescue pancreatic β-cell exocytotic function.
  Similar to compartmentalization of Kv2.1, this present work indicates that exocytotic sites themselves are compartmentalized at “hotspots” in β-cells, and this spatial patterning is impaired in T2D β-cells. Kv2.1 clusters contribute to this compartmentalized exocytosis, in a process that can be regulated by post-translational SUMOylation at the exocytotic site directly.
  This work contributes to a novel knowledge of spatial patterning in human pancreatic β-cells and suggests that Kv2.1 clusters and SUMOylation can be potentially important in the pathogenesis of T2D (208 words).

• Subjects / Keywords

  • Clustering
  • Spatial Patterning of Exocytosis

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3SQ8R03T

• License

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