557-P: Effect of Monocarbonyl Curcumin Analogues C66 and B2BrBC on Pancreatic Expression of Genes Related to Insulin Signaling Pathway and Oxidative Stress in Streptozotocin-Induced Diabetes

Abstract

Curcumin has well documented beneficial effects against diabetes but its poor bioavailability limits its use. Here, we investigated the effects of two monocarbonyl curcumin analogues - (2E,6E) -2,6-bis[ (2-trifluoromethyl) benzylidene]cyclohexanone (C66) and (2E,6E) -2,6-bis (2-bromobenzylidene) cyclohexanone) (B2BrBC) - on the expression of genes involved in insulin signaling and oxidative stress in pancreas samples from streptozotocin (STZ) -induced diabetic rats. Animals were divided into two experiments: (Experiment 1) STZ injection (60 mg/kg) followed by 30 days treatment with C66 or B2BrBC (both 50 µmol/kg, daily) or (Experiment 2) single-dose treated with C66 or B2BrBC (125 µmol/kg) , 6 hours before STZ injection, and sacrifice after 72 hours. Quantitative RT-PCR analysis was used to assess the expression of: insulin (Ins1) , insulin receptor substrate 2 (Irs2) , Slc2a2 solute carrier family 2 member 2 (Slc2a2) (s. Glut2) , mitogen-activated protein kinase 14 (Mapk14) , protein kinase AMP-activated catalytic subunit alpha 1 (Prkaa1) , peroxisome proliferator-activator receptor gamma (Pparg) , BCL2 apoptosis regulator (Bcl2) , BCL2-associated X apoptosis regulator (Bax) , and NF-κB inhibitor alpha (Nfkbia) . Results demonstrated that when C66 and B2BrBC were administered at lower, chronic doses after STZ application (Experiment 1) , they both reversed the effect of STZ on Irs2 mRNA levels in the pancreas, with the effect of C66 being significantly higher. At higher, acute doses (Experiment 2) , C66 ameliorated Ins1 mRNA levels after STZ treatment. Also, although not statistically significant, at higher doses, both C66 and B2BrBC showed a trend to normalize the suppressing effect of STZ on Glut2 mRNA levels. Overall, our data demonstrate that these two monocarbonyl curcumin analogues have direct effects on the expression of insulin signaling pathway-related genes in the pancreas. Disclosure N. Hadzi-Petrushev: None. M. Mladenov: None. J.B. Bogdanov: None. L. Poretsky: None. D. Avtanski: None. Funding Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research