Endoplasmic Reticulum Stress and Diabetes Mellitus.

Abstract

Pancreatic p-cells are strongly engaged in protein secretion and have highly developed endoplasmic reticulum (ER). Proper folding of polypeptide into a threedimensional structure is essential for cellular function and protein malfolding can threaten cell survival.Various conditions can perturb the protein folding in the ER, which is collectively called ER stress. In order to adapt ERstress conditions, the cells respond in three distinct ways such as transcriptional induction of ER chaperones, translational attenuation, and ER-associated degradation (ERAD). However, when ER functions are severely impaired, the cell is eliminated by apoptosis via transcriptional induction of CHOP/GADD153, the activation of CJUNNH2-terminal kinase, and/or the activation of caspase-12. Recent studies have revealed that pcell is one of the most susceptible cells for ERstress, and ERstress-mediated apoptosis in p-cells can be a cause of diabetes. A comprehensive understanding of the impact of the ER stress pathway in p-cells and how it relates to the development of diabetes maycontribute to provide new targets for the prevention and treatment of this disease.

Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis

“…[2][3][4][5] Recent studies show that hepatic ER stress is observed in metabolic diseases such as obesity and diabetes.…”

Too much of a good thing: why it is bad to stimulate the beta cell to secrete insulin

“…Because of its function as a secretory cell, the beta cell is characterised by a highly developed ER and high levels of ER stress transducer proteins, including inositol requirement 1 (IRE1), RNAdependent protein kinase-like ER kinase (PERK) and immunoglobulin heavy chain binding protein (BiP). Studies have shown that the beta cell is one of the most susceptible cells to ER stress, and furthermore, ER stress-mediated apoptosis in the beta cell has been suggested as having an important role in the development of type 2 diabetes [28,29]. In fact, diabetes has been labelled by some as a protein misfolding disease [30], indicating the substantial responsibility the ER has in the correct functioning of the beta cell.…”

Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia

“…High levels of glucose also induce expression of CHOP (C/EBP Homologous protein), which causes a decrease in intracellular pH linked to increased activity of pro-apoptotic protein BAX. 5,6 Increased expression of BAX subsequently aids release of cytochrome c from mitochondria. Prolonged activation of ER stress response activates ER stress induced apoptosis pathway.…”