Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperinsulinemia associated with type II diabetes mellitus (T2DM) is a risk factor for non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Hepatic stellate cells (HSCs) are the major effectors in collagen production during hepatic fibrogenesis. Elevated levels of insulin stimulate HSC activation. In addition to its anti-diabetic effects, the antioxidant curcumin, the yellow pigment in curry from turmeric, suppresses HSC activation and protects the liver from fibrogenesis in vitro and in vivo. This study aims at evaluating the effect of curcumin on insulin-induced HSC activation and further elucidating the underlying mechanisms. We report that curcumin dose-dependently eliminates insulin-induced HSC activation by suppressing expression of type I collagen gene and other key genes relevant to HSC activation. Additional experiments indicate that curcumin interrupts insulin signaling in HSCs by reducing the phosphorylation level of insulin receptor (InsR) and suppressing gene expression of InsR. Furthermore, curcumin attenuates insulin-induced oxidative stress in HSCs by inducing gene expression of glutamate-cysteine ligase (GCL), leading to de novo synthesis of glutathione and the suppression of gene expression of InsR. These results support our initial hypothesis that curcumin inhibits the effects of insulin on stimulating HSC activation by interrupting insulin signaling and attenuating oxidative stress. Our results provide novel insights into the mechanisms by which curcumin inhibits the insulin-induced HSC activation.
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PMID:Curcumin attenuates the effects of insulin on stimulating hepatic stellate cell activation by interrupting insulin signaling and attenuating oxidative stress. 1984 16

Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. Resveratrol was also shown to confer vasoprotection in animal models of type 2 diabetes and aging. However, the mechanisms by which resveratrol exerts its antioxidative vasculoprotective effects are not completely understood. Using a nuclear factor-E(2)-related factor-2 (Nrf2)/antioxidant response element-driven luciferase reporter gene assay, we found that in cultured coronary arterial endothelial cells, resveratrol, in a dose-dependent manner, significantly increases transcriptional activity of Nrf2. Accordingly, resveratrol significantly upregulates the expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1, gamma-glutamylcysteine synthetase, and heme oxygenase-1. Resveratrol treatment also significantly attenuated high glucose (30 mM)-induced mitochondrial and cellular oxidative stress (assessed by flow cytometry using MitoSox and dihydroethidine staining). The aforementioned effects of resveratrol were significantly attenuated by the small interfering RNA downregulation of Nrf2 or the overexpression of Kelch-like erythroid cell-derived protein 1, which inactivates Nrf2. To test the effects of resveratrol in vivo, we used mice fed a high-fat diet (HFD), which exhibit increased vascular oxidative stress associated with an impaired endothelial function. In HFD-fed Nrf2(+/+) mice, resveratrol treatment attenuates oxidative stress (assessed by the Amplex red assay), improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring caspase-3 activity and DNA fragmentation) in branches of the femoral artery. In contrast, the aforementioned endothelial protective effects of resveratrol were diminished in HFD-fed Nrf2(-/-) mice. Taken together, our results indicate that resveratrol both in vitro and in vivo confers endothelial protective effects which are mediated by the activation of Nrf2.
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PMID:Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. 2047 62