Dibenzoylmethane (DBM) is a beta-diketone analog of curcumin. Numerous studies have shown the beneficial effects of curcumin on diabetes, obesity and diabetic complications including diabetic nephropathy. Recently, we investigated the beneficial metabolic effects of DBM on high-fat diet-induced obesity. However, the effects and mechanisms of action of DBM in the kidney are currently unknown. To investigate the renoprotective effects of DBM in type 2 diabetes, we administered DBM (100 mg/kg) orally for 12 weeks to high-fat diet-induced diabetic model mice. We used mouse renal mesangial (MES13) and macrophage (RAW 264.7) cells to examine the mechanism of action of DBM (20 μM). After DBM treatment, the albumin-to-creatinine ratio was significantly decreased compared to that of the high-fat-diet group. Moreover, damaged renal ultra-structures and functions including increased glomerular volume, glomerular basement membrane thickness and inflammatory signals were ameliorated after DBM treatment. Stimulation of MES13 and RAW264.7 cells by palmitate or high-dose glucose with lipopolysaccharides increased inflammatory signals and macrophage migration. However, these changes were reversed by DBM treatment. In addition, DBM inhibited NADPH oxidase 2 and 4 expression and oxidative DNA damage. Collectively, these data suggested that DBM prevented diabetes-induced renal injury through its anti-inflammatory and antioxidant effects.
Eun Soo Lee, Mi-Hye Kwon, Hong Min Kim, Nami Kim, You Mi Kim, Hyeon Soo Kim, Eun Young Lee and Choon Hee Chung
Nami Kim, Jung Ok Lee, Hye Jeong Lee, Yong Woo Lee, Hyung Ip Kim, Su Jin Kim, Sun Hwa Park, Chul Su Lee, Sun Woo Ryoo, Geum-Sook Hwang and Hyeon Soo Kim
Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle.