β-Cell Failure in Type 2 Diabetes: A Case of Asking Too Much of Too Few?

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FIG. 3.
FIG. 3.

Secretory pathway and mechanisms of β-cell defense against protein misfolding. The major β-cell secretory proteins, insulin and IAPP, are synthesized and folded in the ER and then processed within the secretory pathway (Golgi and secretory vesicles). Misfolded proteins are targeted to the ER-associated degradation, also known as ubiquitin-proteasome system (UPS), that involves ubiquitination of the targeted proteins, their deubiquitination by enzymes such as UCH-L1, and subsequent degradation by the proteasome. If the ubiquitin-proteasome system fails or if protein aggregates form, an alternative pathway of protein clearance becomes available: the autophagy pathway in which membranes surround the material to be degraded (ubiquitinated proteins and protein aggregates but also damaged organelles and aged vesicles) to form autophagosomes that fuse with lysosomes to allow degradation of their content.

This Article

  1. Diabetes vol. 62 no. 2 327-335