Abstract
Glucose-induced oxidative stress is associated with the overproduction of reactive oxygen species (ROS), which may dysregulate the expression of genes controlling insulin secretion leading to β-cell dysfunction, a hallmark of type 2 diabetes mellitus (T2DM). This study investigated the impact of coloured rice phenolic extracts (CRPEs) on the expression of key genes associated with β-cell function in pancreatic β-cells (INS-1E). These genes included glucose transporter 2 (Glut2), silent mating type information regulation 2 homolog 1 (Sirt1), mitochondrial transcription factor A (Tfam), pancreatic/duodenal homeobox protein 1 (Pdx-1) and insulin 1 (Ins1). INS-1E cells were cultured in high glucose (25 mM) to induce glucotoxic stress conditions (HGSC) and in normal glucose conditions (NGC-11.1 mM) to represent normal β-cell function. Cells were treated with CRPEs derived from two coloured rice cultivars, Purple and Yunlu29-red varieties at concentrations ranged from 50 to 250 µg/mL. CRPEs upregulated the expression of Glut2, Sirt1 and Pdx-1 significantly at 250 µg/mL under HGSC. CRPEs from both cultivars also upregulated Glut2, Sirt1, Tfam, Pdx-1 and Ins1 markedly at 250 µg/mL under NGC with Yunlu29 having the greatest effect. These data suggest that CRPEs may reduce β-cell dysfunction in T2DM by upregulating the expression of genes involved in insulin secretion pathways.
Highlights
Pancreatic β-cells are the major sites for synthesis, storage and secretion of insulin and amylin, hormones that regulate blood glucose levels
A significant (p < 0.0001) cytotoxic effect on INS-1E cells was observed at 500 and 1000 μg/mL for the Yunlu29 extracts (Figure 1B), reducing cell viability to 66% and 58% respectively post coloured rice phenolic extracts (CRPEs) treatment when compared to the dimethyl sulfoxide (DMSO) control group
Under HGSC, purple phenolic extracts significantly increased the expression of glucose transporter 2 (Glut2) and insulin 1 (Ins1), whereas Yunlu29 extracts significantly increased the expression of Sirt1 and Pancreatic and Duodenal Homeobox-1 (Pdx-1), neither variety affected Tfam expression
Summary
Pancreatic β-cells are the major sites for synthesis, storage and secretion of insulin and amylin, hormones that regulate blood glucose levels. High glucose-induced oxidative stress has been linked with significant damage to cellular molecules including DNA and proteins thereby disrupting cellular signalling and resulting in dysregulation of various genes associated with insulin secretion and β-cell function [3]. The processes leading to insulin release involve the initial glucose entry into β-cells followed by mitochondrial adenosine triphosphate (ATP) generation and K+/Ca2+ membrane depolarisation leading to exocytosis events. These pathways are regulated by some key genes such as Glut, Sirt, Tfam, Pdx-1 and Ins. High glucose-induced stress has been shown to reduce the expression of Glut, severely compromising glucose sensing mechanisms which leads to β-cell dysfunction
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