Biogenesis of Insulin Secretory Granules
A long-standing question in the field of β-cells has been how glucose can very quickly upregulate the overall expression of secretory granule proteins in addition to triggering the fusion of insulin secretory granules. Previous studies have suggested that this induction relies primarily on the activation of post-transcriptional mechanisms, the identity of which, however, has remained unclear.
Klaus' work initially focused on ICA512, a major autoantigen of type I diabetes and a receptor protein tyrosine phosphatase-like protein enriched in insulin secretory granules. We have previously shown that the biosynthesis of ICA512, similar to most other components of secretory granules, is glucose-dependent (Ort et al, 2001). Klaus' work has now unraveled a novel pathway that promotes the concerted expression of ICA512 and most other secretory granule components shortly after glucose stimulation. Such a pathway can explain the ability of β-cells to rapidly restore their pool of secretory granules following stimulation.