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题名:Elevated levels of branched chain amino acids have little effect on pancreatic islet cells but L-arginine impairs function through activation of the endoplasmic reticulum stress response.
作者:MULLOOLY N; VERNON W; SMITH DM; NEWSHOLME P;
来源:Exp Physiol. 2013 Dec 13. [ IF= 0.00 ] ]
URL :10.1113/expphysiol.2013.077495
日期:20140217
摘要:Recent metabolic profiling studies have identified a correlation between
branched-chain amino acid levels, insulin resistance associated with pre-diabetes
and susceptibility to type 2 diabetes. Glucose and lipids in chronic excess have
been reported to induce toxic effects in pancreatic beta cells but the effect of
elevated amino acid concentrations on primary islet cell function has not been
investigated to date. The aim of this study was to investigate the effect of
chronic exposure to various amino acids on islet cell function in vitro. Isolated
rat islets were incubated over periods of 48 hours with increasing concentrations
of individual amino acids (0.1muM-10mM). After 48hr, islets were assessed for
glucose dependent insulin secretion capacity, proliferation or islet cell
apoptosis. We report that elevated levels of branched chain amino acids have
little effect on pancreatic islet cell function or viability, however increased
levels of the amino acid L-arginine were found to be beta cell toxic, causing a
dose dependent decrease in insulin secretion accompanied by a decrease in islet
cell proliferation and an increase in islet cell apoptosis. These effects were
not due to L-arginine dependent increases in production of nitric oxide but
through elicitation of the islet cell endoplasmic stress (ER) response. This
novel finding indicates for the first time that L-arginine concentration in vitro
may impact negatively on islet cell function thus indicating further complexity
in relation to in vivo susceptibility of beta-cells towards nutrient induced
dysfunction.

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