Consumption of a western diet and the pancreatic O‐GlcNAc response

Abstract

Consumption of high fat diets typically result in insulin resistance and elevated circulating insulin levels; however, recent rodent studies have demonstrated that a western diet high in both fat and carbohydrate depresses insulin levels. It has been suggested that increased protein levels of β‐N‐acetyl‐glucosamine (O‐GlcNAc) promotes β‐cell dysfunction. Therefore, the aim of this study was to examine the effects of short‐term consumption of a western diet on the pancreas. Young male rats received control (CON; 12% kcal fat/19% protein/69% carbohydrate) or western (WES; 40/15/45%) diets for 2 weeks. Insulin sensitivity was 34% and plasma insulin 50% lower in WES whereas blood glucose remained similar between groups (6.5 ± 0.2 mmol/l CON vs 6.0 ± 0.2 mmol/l WES). At the protein level, there was no evidence of accumulation of advanced glycation end‐products (AGE) or endoplasmic reticulum stress (HSP47, GRP78) in WES and there were negligible levels of TUNEL‐positive cells in both groups. Histological analyses revealed decreased levels of protein O‐GlcNAcylation in WES compared to CON in both islet and non‐islet regions of the pancreas with equivalent levels of insulin staining and islet size. These data suggest that decreased protein O‐GlcNAcylation may contribute to dysregulation of insulin production and/or secretion in the pancreas following short‐term consumption of a western diet.