Skip to main content
. Author manuscript; available in PMC: 2016 Apr 1.
Published in final edited form as: Mol Aspects Med. 2015 Jan 8;42:105–118. doi: 10.1016/j.mam.2015.01.001

Figure 4. Primary and secondary proinsulin misfolding and beta cell failure.

Figure 4

Proinsulin misfolding can be caused by Ins gene mutations, in which the misfolded proinsulin generates a “first hit” leading to ER stress and beta cell failure. In other cases, alterations in the ER folding environment can adversely affect the folding of wild-type proinsulin, leading to an increase of proinsulin misfolding. These misfolded proinsulin molecules may further impair the ER folding environment, providing a “second hit” that aggravates ER dysfunction and leads to beta cell failure.