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. 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 5. Hypothetical model illustrating the progression of beta cell failure as a consequence of increased proinsulin misfolding.

Figure 5

During the development and progression of diabetes, increased proinsulin misfolding (red arrow) caused by genetic and environmental factors can induce ER stress and decrease insulin production (blue arrow). As misfolded proinsulin exceeds the genetically-determined threshold (dashed line) that beta cells can handle the misfolded protein load, diabetes occurs. Elevated blood glucose further stimulates proinsulin biosynthesis, producing more misfolded proinsulin load in the ER, aggravating ER stress and beta cell failure.