| First Author | Sampath C | Year | 2019 |
| Journal | Free Radic Biol Med | Volume | 135 |
| Pages | 132-143 | PubMed ID | 30831189 |
| Mgi Jnum | J:292663 | Mgi Id | MGI:6445434 |
| Doi | 10.1016/j.freeradbiomed.2019.02.029 | Citation | Sampath C, et al. (2019) Activation of Nrf2 attenuates delayed gastric emptying in obesity induced diabetic (T2DM) female mice. Free Radic Biol Med 135:132-143 |
| abstractText | Diabetic gastroparesis (GP) is a clinical syndrome characterized by delayed gastric emptying (DGE). Loss of Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) led to reduced nNOSalpha mediated gastric motility and DGE. The molecular signaling of cinnamaldehyde (CNM) mediated Nrf2 activation and its mechanistic role on DGE were further investigated in obese/T2D female mice. Adult female homozygous Nfe2l2(-/-) (C57BL/6J) and their wild-type (WT) littermates (Nfe2l2(+/+)) mice were fed with high fat diet (HFD; Obese/T2D model), or normal diet (ND) with or without CNM (50mg/kg b.w; i.p). Supplementation of CNM attenuated (p<0.05) DGE in WT female but not in Nrf2 KO Obese/T2D mice. CNM (1) normalized serum estradiol-17beta levels, (2) induced gastric Nrf2 and phase II antioxidant enzymes through extracellular signal-regulated kinase, (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK), (3) reduced glucose synthase kinase 3 beta (GSK3beta) and aryl hydrocarbon receptor (AhR) and this was associated with (4) increased estrogen receptor expression, BH4 (Cofactor of nNOS) biosynthesis enzyme GCH-1 and nNOSalpha dimerization in WT Obese/T2 diabetic female mice. In addition, CNM restored impaired nitrergic relaxation in hyperglycemic conditions. These findings emphasize the importance of Nrf2 in maintaining nNOSalpha mediated GE and may have a translational relevance to treat obese/diabetic gastroparesis in women. |
