title: Endoplasmic reticulum stress in insulin resistance and diabetes.
abstract: The endoplasmic reticulum is the main intracellular Ca(2+) store for Ca(2+) release during cell signaling. There are different strategies to avoid ER Ca(2+) depletion. Release channels utilize first Ca(2+)-bound to proteins and this minimizes the reduction of the free luminal [Ca(2+)]. However, if release channels stay open after exhaustion of Ca(2+)-bound to proteins, then the reduction of the free luminal ER [Ca(2+)] (via STIM proteins) activates Ca(2+) entry at the plasma membrane to restore the ER Ca(2+) load, which will work provided that SERCA pump is active. Nevertheless, there are several noxious conditions that result in decreased activity of the SERCA pump such as oxidative stress, inflammatory cytokines, and saturated fatty acids, among others. These conditions result in a deficient restoration of the ER [Ca(2+)] and lead to the ER stress response that should facilitate recovery of the ER. However, if the stressful condition persists then ER stress ends up triggering cell death and the ensuing degenerative process leads to diverse pathologies; particularly insulin resistance, diabetes and several of the complications associated with diabetes. This scenario suggests that limiting ER stress should decrease the incidence of diabetes and the mobility and mortality associated with this illness.
authors.affiliation: Departamento de Bioquímica, Cinvestav, Mexico City 07000, Mexico. Electronic address: aguerrero@cinvestav.mx.
authors.forename: Agustin
authors.initials: A
authors.lastname: Guerrero-Hernández
authors.affiliation: Departamento de Bioquímica, Cinvestav, Mexico City 07000, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Leon-Aparicio
authors.affiliation: Departamento de Bioquímica, Cinvestav, Mexico City 07000, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Chavez-Reyes
authors.affiliation: Departamento de Bioquímica, Cinvestav, Mexico City 07000, Mexico.
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Olivares-Reyes
authors.affiliation: Departamento de Bioquímica, Cinvestav, Mexico City 07000, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: DeJesus
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium
keywords: Ca(2+) leak; Diabetes; ER stress; Endoplasmic reticulum; Endothelial cells; Insulin resistance; SERCA pump