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. Author manuscript; available in PMC: 2011 Dec 1.
Published in final edited form as: Trends Endocrinol Metab. 2010 Sep 17;21(12):714–721. doi: 10.1016/j.tem.2010.08.005

Figure 4.

Figure 4

Glucose dynamically regulates PERK activity in the insulin secreting beta cell. Within the normal physiological range of serum glucose, PERK activity is relatively high after an overnight fast but is rapidly reduced by the administration of high glucose (19). We hypothesize that increased PERK activity during fasting (low glucose) increases quality control that serves to limit the anterograde trafficking proinsulin and insulin secretion. However, sustained high levels of circulating glucose negatively impact the function of beta cells, and a high level of PERK activity is seen. We speculate that one of the consequences of glucotoxicity is the accumulation of unfolded proteins in the ER that activate PERK and the other arms of the ER stress pathway.