Frontiers in Pharmacology (Aug 2016)
Effects of tocotrienols on insulin secretion-associated genes expression of rat pancreatic islets in a dynamic culture
Abstract
Tocotrienols (T3) are well known for their antioxidant properties besides showing therapeutic potential in clinical complications such as hyperlipidemia induced by diabetes. The aim of this study was to determine the effects of δ-T3, γ-T3 and α-T3 on insulin secretion-associated genes expression of rat pancreatic islets in a dynamic culture. Pancreatic islets freshly isolated from male Wistar rats were treated with T3 for 1 h at 37oC in a microfluidic system with continuous operation. The cells were collected for total RNA extraction and reverse-transcribed, followed by measurement of insulin secretion-associated genes expression using quantitative real-time polymerase chain reaction (qRT-PCR). Molecular docking experiments were performed to gain insights on how the T3 bind to the receptors. Short-term exposure of δ- and γ-T3 to pancreatic β cells in a stimulant glucose condition (16.7 mM) significantly regulated preproinsulin mRNA levels and insulin gene transcription. In contrast, α-T3 possessed less ability in the activation of insulin synthesis level. Essentially, potassium chloride (KCl), a β cell membrane depolarising agent added into the treatment further enhanced the insulin production. δ- and γ-T3 revealed significantly higher quantitative expression in most of the insulin secretion-associated genes groups containing 16.7 mM glucose alone and 16.7 mM glucose with 30 mM KCl ranging from 600 to 1200 µM (p < 0.05). The findings suggest the potential of δ-T3 in regulating insulin synthesis and glucose-stimulated insulin secretion through triggering pathway especially in the presence of KCl.
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