Taurine Supplementation Restores Insulin Secretion and Reduces ER Stress Markers in Protein-Malnourished Mice - Advances in Experimental Medicine and Biology - page 123

In conclusion, malnutrition leads to impaired islet function which is restored
with TAU supplementation possibly by increasing survival signals and lowering ER
stress proteins. Lower ER stress markers in the liver may also contribute to the
improvement of insulin action on peripheral organs.

Abbreviations

ATF4 Activating transcription factor 4

BIP Binding immunoglobulin protein

CHOP C / EBP homologous protein

ER Endoplasmic reticulum

ERK1/2 Extracellular signal-regulated kinase

IRE-1 Inositol-requiring enzyme-1

PERK PKR-like ER kinase

SERCA Sarco(endo)plasmic reticulum Ca 2+ -ATPase

TAU Taurine

14.1 Introduction

The ER is a highly specialized organelle where newly synthesized proteins are
folded into their tridimensional structure which is crucial for their biological activ-
ity (Hotamisligil 2010 ). ER stress is a cellular response activated by the intra-reticular
accumulation of misfolded proteins due to increased protein synthesis or poor ER
function. Adequate protein folding is dependent on ER Ca 2+ stores that are main-
tained by the sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) pump that
actively transports Ca 2+ from the cytoplasm to the ER lumen (Eizirik et al. 2008 ) .
In fact, ER Ca 2+ depletion using SERCA pump inhibitors such as thapsigargin
leads to impaired protein folding capacity and activation of ER stress response
initiated by the ER membrane-residing proteins PKR-like ER kinase (PERK),
inositol-requiring enzyme-1 (IRE1), and activating transcription factor-6 (ATF6)
(Lytton et al. 1991 ; Lin et al. 2008 ). In addition, ER stress immediately inhibits
protein synthesis that occurs through the PERK/eIF2/ATF4 branch of this pathway.
Persistence of the stressing conditions increases the expression of the transcription
factor C/EBP homologous protein (CHOP) leading to cell death via apoptosis
(Hotamisligil 2010 ) .
Poor nutrition during gestation and early life can predispose to the development
of metabolic disturbances in adulthood such as hypertension, obesity, and type 2
diabetes mellitus (Remacle et al. 2007 ). Previous studies showed that low-birth-
weight children had increased risk for becoming insulin resistant in adulthood
(Hales and Barker 1992 ; Jaquet et al. 2000 ). Increased ER stress was already
reported in protein malnutrition (Sparre et al. 2003 ; Vo and Hardy 2012 ) as well as