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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. 2014 Mar;99(3):538-51. doi: 10.1113/expphysiol.2013.077495. Epub [ IF= 0.00 ] ]
URL :10.1113/expphysiol.2013.077495
日期:20140408
摘要:Recent metabolic profiling studies have identified a correlation between
branched-chain amino acid levels, insulin resistance associated with prediabetes
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 h with a range of concentrations of
individual amino acids (0.1 mum to 10 mm). After 48 h, 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 arose
through elicitation of the islet cell endoplasmic reticulum stress response. This
novel finding indicates, for the first time, that the l-arginine concentration in
vitro may impact negatively on islet cell function, thus indicating further
complexity in relationship to in vivo susceptibility of beta-cells to
nutrient-induced dysfunction.

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