(p-ClPhSe)2 stimulates carbohydrate metabolism and reverses the metabolic alterations induced by high fructose load in rats

Food Chem Toxicol. 2017 Sep;107(Pt A):122-128. doi: 10.1016/j.fct.2017.06.038. Epub 2017 Jun 24.

Abstract

The modern life leads to excess consumption of food rich in fructose; however, the long-term changes in carbohydrate and lipid metabolism could lead to metabolic dysfunction in humans. The present study evaluated the in vitro insulin-mimetic action of p-chloro-diphenyl diselenide (p-ClPhSe)2. The second aim of this study was to investigate if (p-ClPhSe)2 reverses metabolic dysfunction induced by fructose load in Wistar rats. The insulin-mimetic action of (p-ClPhSe)2 at concentrations of 50 and 100 μM was determined in slices of rat skeletal muscle. (p-ClPhSe)2 at a concentration of 50 μM stimulated the glucose uptake by 40% in skeletal muscle. A dose-response curve revealed that (p-ClPhSe)2 at a dose of 25 mg/kg reduced (∼20%) glycemia in rats treated with fructose (5 g/kg, i.g.). The administration of fructose impaired the liver homeostasis and (p-ClPhSe)2 (25 mg/kg) protected against the increase (∼25%) in the G-6-Pase and isocitrate dehydrogenase activities and reduced the triglyceride content (∼25%) in the liver. (p-ClPhSe)2 regulated the liver homeostasis by stimulating hexokinase activity (∼27%), regulating the TCA cycle activity (increased the ATP and citrate synthase activity (∼15%)) and increasing the glycogen levels (∼67%). In conclusion, (p-ClPhSe)2 stimulated carbohydrate metabolism and reversed metabolic dysfunction in rats fed with fructose.

Keywords: Diselenide; Fructose; Insulin-mimetic action; Metabolism; Organoselenium.

MeSH terms

  • Animals
  • Carbohydrate Metabolism / drug effects*
  • Fructose / adverse effects*
  • Fructose / metabolism
  • Hexokinase / metabolism
  • Homeostasis / drug effects
  • Humans
  • Isocitrate Dehydrogenase / metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Metabolic Diseases / drug therapy*
  • Metabolic Diseases / enzymology
  • Metabolic Diseases / etiology
  • Metabolic Diseases / metabolism
  • Organoselenium Compounds / administration & dosage*
  • Rats
  • Rats, Wistar
  • Triglycerides / metabolism

Substances

  • Organoselenium Compounds
  • Triglycerides
  • p-chloro-diphenyl diselenide
  • Fructose
  • Isocitrate Dehydrogenase
  • Hexokinase