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Blockage of MyD88 in cardiomyocytes alleviates cardiac inflammation and cardiomyopathy in experimental diabetic mice
In this study, we first found that MyD88 expression was increased in cardiomyocytes of diabetic mouse hearts. In cultured cardiomyocytes, MyD88 inhibition either by siRNA or by small-molecular inhibitor LM8 markedly blocked TLR4-MyD88 complex formation, reduced pro-inflammatory mitogen-activated protein kinases/nuclear factor-κB (MAPKs/NF-κB) cascade activation and decreased pro-inflammatory cytokine expression under high glucose condition. Moreover, pharmacologic inhibition of MyD88 by LM8 showed significantly anti-inflammatory, anti-hypertrophic and anti-fibrotic effects in the hearts of both type 1 and type 2 diabetic...
Source: Biochemical Pharmacology - October 14, 2022 Category: Drugs & Pharmacology Authors: Wu Luo Gaojun Wu Xiaojun Chen Qiuyan Zhang Chunpeng Zou Jun Wang Jun Liu Nipon Chattipakorn Yi Wang Guang Liang Source Type: research

Resolvin D3 improves the impairment of insulin signaling in skeletal muscle and nonalcoholic fatty liver disease through AMPK/autophagy-associated attenuation of ER stress
Biochem Pharmacol. 2022 Aug 7:115203. doi: 10.1016/j.bcp.2022.115203. Online ahead of print.ABSTRACTResolvin D3 (RD3), an endogenous lipid mediator derived from omega-3 fatty acids, has been documented to attenuate inflammation in various disease models. Although it has been reported that omega-3 fatty acids attenuate metabolic disorders, the roles of RD3 in insulin signaling in skeletal muscle and hepatic lipid metabolism remain unclear. In the current study, we examined the role of RD3 in skeletal muscle insulin resistance and hepatic steatosis using in vitro and in vivo obesity models. In mouse primary hepatocytes, RD3 ...
Source: Biochemical Pharmacology - August 10, 2022 Category: Drugs & Pharmacology Authors: Heeseung Oh Wonjun Cho A M Abd El-Aty Cemil Bayram Ji Hoon Jeong Tae Woo Jung Source Type: research

Modulation of Sirt1/NF- κB interaction of evogliptin attributed to inhibition of vascular inflammatory response leading to attenuation of atherosclerotic plaque formation.
This study demonstrates that the protective effect of evogliptin on atherosclerotic progression via inhibition of vascular inflammation. The findings imply that evogliptin has potential for anti-atherosclerosis therapy that targets arterial inflammation. PMID: 31421133 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - August 13, 2019 Category: Drugs & Pharmacology Authors: Anh Nguyen P, Soon Won J, Khalilur Rahman M, Ju Bae E, Kyung Cho M Tags: Biochem Pharmacol Source Type: research

Pioglitazone, a PPARγ agonist, attenuates PDGF-induced vascular smooth muscle cell proliferation through AMPK-dependent and AMPK-independent inhibition of mTOR/p70S6K and ERK signaling.
Abstract Pioglitazone (PIO), a PPARγ agonist that improves glycemic control in type 2 diabetes through its insulin-sensitizing action, has been shown to exhibit beneficial effects in the vessel wall. For instance, it inhibits vascular smooth muscle cell (VSMC) proliferation, a major event in atherosclerosis and restenosis after angioplasty. Although PPARγ-dependent and PPARγ-independent mechanisms have been attributed to its vasoprotective effects, the signaling events associated with PIO action in VSMCs are not fully understood. To date, the likely intermediary role of AMP-activated protein kinase (AMPK) towar...
Source: Biochemical Pharmacology - November 28, 2015 Category: Drugs & Pharmacology Authors: Osman I, Segar L Tags: Biochem Pharmacol Source Type: research

AMP-Activated Protein Kinase as Regulator of P2Y6 Receptor-Induced Insulin Secretion in Mouse Pancreatic β-Cells.
Abstract 5'-AMP-activated protein kinase (AMPK) and its pharmacological modulators have been targeted for treating type 2 diabetes. Extracellular uridine 5'-diphosphate (UDP) activates P2Y(6) receptors (P2Y(6)Rs) in pancreatic β-cells to release insulin and reduce apoptosis, which would benefit diabetes. Here, we studied the role of P2Y(6)R in activation of AMPK in MIN6 mouse pancreatic β-cells and insulin secretion. Treatment with a potent P2Y(6)R dinucleotide agonist MRS2957 (500nM) activated AMPK, which was blocked by P2Y(6)R-selective antagonist MRS2578. Also, MRS2957 induced phosphorylation of acetyl-coenzy...
Source: Biochemical Pharmacology - January 17, 2013 Category: Drugs & Pharmacology Authors: Balasubramanian R, Maruoka H, Jayasekara MP, Gao ZG, Jacobson KA Tags: Biochem Pharmacol Source Type: research

Metformin-mediated downregulation of p38 mitogen-activated protein kinase-dependent excision repair cross-complementing 1 decreases DNA repair capacity and sensitizes human lung cancer cells to paclitaxel.
Abstract Metformin, an extensively used and well-tolerated drug for treating individuals with type 2 diabetes, has recently gained significant attention as an anticancer drug. On the other hand, paclitaxel (Taxol) is a new antineoplastic drug that has shown promise in the treatment of non-small cell lung cancer (NSCLC). High expression levels of excision repair cross-complementary 1 (ERCC1) in cancers have been positively associated with the DNA repair capacity and a poor prognosis in NSCLC patients treated with platinum-containing chemotherapy. In this current study, paclitaxel was found to increase phosphorylati...
Source: Biochemical Pharmacology - December 7, 2012 Category: Drugs & Pharmacology Authors: Tseng SC, Huang YC, Chen HJ, Chiu HC, Huang YJ, Wo TY, Weng SH, Lin YW Tags: Biochem Pharmacol Source Type: research