Correlation Engine 2.0
Clear Search sequence regions


  • antibodies (1)
  • brefeldin (1)
  • donors (1)
  • glucagon (1)
  • human (2)
  • human cells (4)
  • insulin (3)
  • mice (2)
  • pathogenesis (1)
  • patients (1)
  • PC 1 (3)
  • PCSK2 (2)
  • proglucagon (2)
  • proinsulin (11)
  • protein human (1)
  • Sizes of these terms reflect their relevance to your search.

    Insulin is first produced in pancreatic β-cells as the precursor prohormone proinsulin. Defective proinsulin processing has been implicated in the pathogenesis of both type 1 and type 2 diabetes. Though there is substantial evidence that mouse β-cells process proinsulin using prohormone convertase 1/3 (PC1/3) and then prohormone convertase 2 (PC2), this finding has not been verified in human β-cells. Immunofluorescence with validated antibodies revealed that there was no detectable PC2 immunoreactivity in human β-cells and little PCSK2 mRNA by in situ hybridization. Similarly, rat β-cells were not immunoreactive for PC2. In all histological experiments, PC2 immunoreactivity in neighboring α-cells acted as a positive control. In donors with type 2 diabetes, β-cells had elevated PC2 immunoreactivity, suggesting that aberrant PC2 expression may contribute to impaired proinsulin processing in β-cells of patients with diabetes. To support histological findings using a biochemical approach, human islets were used for pulse-chase experiments. Despite inhibition of PC2 function by temperature blockade, brefeldin A, chloroquine, and multiple inhibitors that blocked production of mature glucagon from proglucagon, β-cells retained the ability to produce mature insulin. Conversely, suppression of PC1/3 blocked processing of proinsulin but not proglucagon. By demonstrating that healthy human β-cells process proinsulin by PC1/3 but not PC2, we suggest that there is a need to revise the long-standing theory of proinsulin processing. © 2020 by the American Diabetes Association.

    Citation

    Adam Ramzy, Ali Asadi, Timothy J Kieffer. Revisiting Proinsulin Processing: Evidence That Human β-Cells Process Proinsulin With Prohormone Convertase (PC) 1/3 but Not PC2. Diabetes. 2020 Jul;69(7):1451-1462

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 32291281

    View Full Text