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. 2010 May 27;25(2):111–118. doi: 10.1007/s12291-010-0022-1

Endoplasmic reticulum stress in diabetes: New insights of clinical relevance

Muthuswamy Balasubramanyam 1,✉, Raji Lenin 1, Finny Monickaraj 1
PMCID: PMC3453102  PMID: 23105896

Abstract

The endoplasmic reticulum (ER) is a cellular compartment responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. A myriad of pathological and physiological factors perturb ER function and cause dysregulation of ER homeostasis, leading to ER stress. Accumulating evidence suggests that ER stress plays a role in the pathogenesis of diabetes, contributing to pancreatic β-cell loss and insulin resistance. ER stress may also link obesity, inflammation and insulin resistance in type 2 diabetes. In this review, we address the transition from physiology to pathology, namely how and why the physiological UPR evolves to a proapoptotic ER stress response in diabetes and its complications. Special attention was given to elucidate how ER stress could explain some of the ‘clinical paradoxes’ such as secondary sulfonylurea failure, initial worsening of retinopathy during tight glycemic control, insulin resistance induced by protease inhibitors and other clinically relevant observations.

Key Words: ER stress, UPR, diabetes, glucolipotoxicity, autophagy, glycemic variability

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