Novel Triterpenoids from Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats.

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased ( < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner ( < 0.05). Plasma insulin ( < 0.0001)/C-peptide ( < 0.0006), tissue glycogen ( < 0.0034), glycogen phosphorylase ( < 0.005), glucose 6-phosphatase ( < 0.0001) and lipid markers were significantly increased ( < 0.0001) in diabetic rats, whereas glucokinase ( < 0.0047), glycogen synthase ( < 0.003), glucose oxidation ( < 0.001), GLUT4 mRNA ( < 0.0463), GLUT4 protein ( < 0.0475) and the insulin-signaling molecules IR mRNA ( < 0.0195), IR protein ( < 0.0001), IRS-1 mRNA ( < 0.0478), p-IRS-1 ( < 0.0185), Akt mRNA ( < 0.0394), p-Akt ( < 0.0162), GLUT4 mRNA ( < 0.0463) and GLUT4 ( < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1-C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1-C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.