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 37°C 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. 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.
Highlights
Insulin is the most potent anabolic hormone secreted by the pancreatic islets of Langerhans of β cell
Data collected from qRT-PCR showed the relative gene expression level of insulin secretion-associated gene, the relationship between the ligand-modulated transcription factors, insulin release gene and insulin gene transcription factor
The gene expression analysis in tocotrienol treatments suggested an important role of tocotrienol derivatives in the activation of insulin transcription factors following an impact on insulin secretion
Summary
Insulin is the most potent anabolic hormone secreted by the pancreatic islets of Langerhans of β cell. The chronic complications of diabetes mellitus lead to a progressive deterioration in the function of pancreatic β cell and development of Tocotrienols on Insulin Genes Expression hyperglycemia (Bösenberg and van Zyl, 2008) with long-term clinical problems and onset of chronic complications (Niu et al, 2008). T3 consist of lipid-soluble farnesyl side-chain that provides the added advantage for the differential membrane distribution and metabolism of T3 as compared to tocopherols (Theriault et al, 1999; Vignini et al, 2011). In contrast to their structural similarity, the methyl group position determines the individual compound (Figure 1) (Passwater, 2012). Studies had proven that T3 functioned as signaling molecule in antioxidant properties with α-T3 having 40–60 times more potent antioxidative protection than α-tocopherol in rat liver lipid (Serbinova et al, 1991; Tan, 2005)
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