(p-ClPhSe)2 modulation on carbohydrate and lipid metabolism requires the insulin-like signaling in Caenorhabditis elegans
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS(2024)
Abstract
Organoselenium compounds modulate the metabolism by regulating carbohydrate and lipid syntheses and degradation in the liver, muscle, and adipose tissue. Notably, p-chloro-diphenyl diselenide (p-ClPhSe)(2) can directly regulate the activities of enzymes involved in glucose metabolism, suggesting an insulin-like effect in rodents; however, there is still a lack of scientific evidence to confirm this hypothesis. The objective of this study was to investigate (p-ClPhSe)(2) effects on glucose and lipid metabolism in Caenorhabditis elegans. The contribution of AGE-1/PI3K, AKT -1, AKT -2, PFK-1, DAF-16, and DAF-2 in the (p-ClPhSe)2 effects were also investigated. Our results demonstrate that (p-ClPhSe)2 acute exposure presented some toxicity to the worms, and therefore, lower concentrations were further used. (p-ClPhSe)(2) reduced glucose and triglyceride levels to the baseline levels, after induction with glucose or fructose, in wild -type worms. This effect required proteins involved in the insulin/IGF1 like signaling, such as the DAF-2, AGE-1, AKT -1 and AKT -2, PFK-1, but also DAF-16, which would be negatively regulated by DAF-2 activation. Moreover, the reduction in glucose and triglyceride levels, caused by (p-ClPhSe)2 per se was lost in age-1/daf-16 worms, suggesting that insulin/IGF-1-like signaling in a DAF-2 and AGE-1/DAF-16 dependent-manner in C. elegans are necessary to effects of (p-ClPhSe)(2). In conclusion, (p-ClPhSe)(2) requires proteins involved in the IIS pathway to modulate carbohydrate and lipid metabolism.
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Key words
Organoselenium compound,Insulin pathway,Glucose,Triglycerides,Glycogen
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