[HYPOLIPIDEMIC, ANTIOXIDANT, AND ENDOTHELIAL PROTECTIVE EFFECT OF COMPOUND ZB-16 (NOVEL GPR119 RECEPTOR AGONIST) IN RATS WITH EXPERIMENTAL TYPE 2 DIABETES]

Eksp Klin Farmakol. 2017;80(1):18-23.
[Article in Russian]

Abstract

The effect of compound ZB-16 (a new GPR1 19 receptor agonist) after two-week administration on the endothelial function, glucose and lipid metabolism (total cholesterol, LDL, HDL and triglycerides), lipid peroxidation, and antioxidant system status in rats with experimental type-2 diabetes mellitus (T2DM) has been studied. It was found that the untreated control group of animals exhibited, in addition to sustained hyperglycemia, a decrease in endothelium-dependent vaso- dilation and antioxidant system activity, and increase in the content of LDL and the dyslipidemic index. Administration of ZB-16 (1 mg/kg, p.o.) in rats with T2DM model resulted in reduction of the endothelial dysfunction (improved endothelium-dependent vasodilation by 83% as compared to the control group, p < 0.05). ZB-16 also produced a moderate antioxidant effect of reducing the content of TBA-active products (by 30% as compared to the untreated control, p <0.05) and favored normalization of lipid metabolism indicators.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cell Count
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Dyslipidemias / blood
  • Dyslipidemias / chemically induced
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / genetics
  • Endothelial Cells / drug effects
  • Female
  • Gene Expression / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Hypolipidemic Agents / pharmacology*
  • Hypolipidemic Agents / therapeutic use
  • Lipid Metabolism / drug effects
  • Lipid Peroxidation / drug effects
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Streptozocin
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Triglycerides / blood
  • Vasodilation / drug effects

Substances

  • Antioxidants
  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • GPR119 protein, rat
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Piperidines
  • Pyrimidines
  • Receptors, G-Protein-Coupled
  • Thiobarbituric Acid Reactive Substances
  • Triglycerides
  • Streptozocin