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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
Published on: January 23, 2018
Allyl isothiocyanate ameliorates insulin resistance through the regulation of mitochondrial function
Jiyun Ahn1, Hyunjung Lee2, Sung Won Im2
1Metabolism and Nutrition Research Group, Korea Food Research Institute, Seoungnam, Korea; Division of Food Biotechnology, Korea University of Science and Technology, Daejeon, Korea.
Abstract:
Mitochondrial dysfunction is associated with the pathophysiology of insulin resistance. Allylisothiocyanate (AITC) is found in many cruciferous vegetables and has been reported to possess anticancer activity. However, the effect of AITC on insulin resistance and mitochondrial function has not yet been investigated. Here, we show that AITC increased glucose uptake in insulin-resistant C2C12 myotubes and augmented glucose transporter 4 (GLUT4) translocation in L6-GLUT4myc cells. AITC recovered the impaired insulin signaling evoked by free fatty acid exposure and increased mitochondrial membrane potential and mitochondrial DNA content. AITC also elevated the rate of oxygen consumption in C2C12 cells. Furthermore, mice that were fed a high-fat diet with AITC for 10 weeks had reduced diet-induced obesity and hepatic steatosis. AITC also inhibited the hyperglycemia and hyperinsulinemia induced by the consumption of a high-fat diet. Glucose and insulin tolerance tests indicated that AITC improved both glucose tolerance and insulin sensitivity. In addition, AITC inhibited hepatic gluconeogenesis and ameliorated high fat diet-induced mitochondrial dysfunction. Collectively, these data suggest that the protective effect of AITC on insulin resistance is partly mediated through the modulation of mitochondrial dysfunction.
Insights
Allyl isothiocyanate (AITC) improves insulin resistance by enhancing glucose uptake and restoring mitochondrial function. This compound, found in cruciferous vegetables, combats diet-induced obesity and metabolic dysfunction.
Area of Science:
- Biochemistry
- Metabolism
- Cell Biology
Background:
- Mitochondrial dysfunction is a key factor in insulin resistance.
- Allyl isothiocyanate (AITC), derived from cruciferous vegetables, is known for anticancer properties.
- The impact of AITC on insulin resistance and mitochondrial health remains unexplored.
Purpose of the Study:
- To investigate the effects of AITC on insulin resistance and mitochondrial function.
- To determine if AITC can ameliorate metabolic disturbances associated with high-fat diets.
Main Methods:
- Assessed AITC's effect on glucose uptake and glucose transporter 4 (GLUT4) translocation in cell models (C2C12 myotubes, L6-GLUT4myc cells).
- Evaluated AITC's impact on insulin signaling, mitochondrial membrane potential, mitochondrial DNA content, and oxygen consumption.
- Administered AITC to mice on a high-fat diet, monitoring for changes in obesity, hepatic steatosis, hyperglycemia, and hyperinsulinemia.
- Conducted glucose and insulin tolerance tests in mice to assess metabolic improvements.
- Analyzed AITC's effect on hepatic gluconeogenesis and mitochondrial function in vivo.
Main Results:
- AITC enhanced glucose uptake and GLUT4 translocation in insulin-resistant cells.
- AITC restored impaired insulin signaling, increased mitochondrial membrane potential, and boosted mitochondrial DNA content and oxygen consumption.
- AITC administration reduced diet-induced obesity, hepatic steatosis, hyperglycemia, and hyperinsulinemia in mice.
- AITC significantly improved glucose tolerance and insulin sensitivity in mice.
- AITC inhibited hepatic gluconeogenesis and mitigated high-fat diet-induced mitochondrial dysfunction.
Conclusions:
- AITC demonstrates significant potential in combating insulin resistance.
- The beneficial effects of AITC are partly attributed to its ability to modulate mitochondrial dysfunction.
- AITC shows promise as a therapeutic agent for metabolic disorders linked to mitochondrial impairment.
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