title: Endoplasmic reticulum stress and glucose homeostasis.
abstract: OBJECTIVE
  Balancing glucose homeostasis is crucial to maintain appropriate energy and metabolic state. Chronic hyperglycemia with insulin resistance and development of type II diabetes mellitus is a growing health and health-economic threat. The unfolded protein response (UPR) is a mechanism by which the endoplasmic reticulum copes with diverse physiological and pathophysiological stress stimuli. Unresolved and chronic endoplasmic reticulum stress are important features in the development of diabetes mellitus. Understanding how the UPR impacts glucose balance and what disrupts this balance is critical for development of future therapies.
  
  
  RESULTS
  In pancreatic β-cells, evidence is growing that the single branches of the UPR work in concert to supply insulin in response to acute glucose availability. Chronic glucose stimulation disrupts these primarily adaptive changes into an overwhelming UPR, which leads to reduced insulin supply and β-cell mass due to apoptosis. In hepatocytes, the UPR interacts with key transcription factors to physiologically regulate glucose and lipid homeostasis. Prolonged endoplasmic reticulum stress disrupts these feedback loops and results in ongoing gluconeogenesis and steatosis.
  
  
  CONCLUSIONS
  Unraveling the molecular networks underlying the adaptive and contra-adaptive roles of the UPR in glucose metabolism will identify novel therapeutic approaches in the battle against diabetes mellitus.
authors.affiliation: Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Wagner
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
mesh_terms: D000818:Animals; D017209:Apoptosis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D013312:Stress, Physiological; D056811:Unfolded Protein Response
chemical_list: D007328:Insulin; D005947:Glucose