Skip Navigation LinksHome > July 2011 - Volume 14 - Issue 4 > Endoplasmic reticulum stress and glucose homeostasis
Current Opinion in Clinical Nutrition & Metabolic Care:
doi: 10.1097/MCO.0b013e32834778d4
Carbohydrates: Edited by Luc Tappy and Bettina Mittendorfer

Endoplasmic reticulum stress and glucose homeostasis

Wagner, Martina,b; Moore, David Db

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Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

© 2011 Lippincott Williams & Wilkins, Inc.

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