scholarly journals Inhibition of Adenosine Monophosphate-Activated Protein Kinase-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Signaling Leads to Hypercholesterolemia and Promotes Hepatic Steatosis and Insulin Resistance

2018 ◽  
Vol 3 (1) ◽  
pp. 84-98 ◽  
Author(s):  
Kim Loh ◽  
Shanna Tam ◽  
Lisa Murray-Segal ◽  
Kevin Huynh ◽  
Peter J. Meikle ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Hepatic Steatosis ◽  
Coenzyme A ◽  
Adenosine Monophosphate ◽  
Coenzyme A Reductase

scholarly journals Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1024 ◽  
Author(s):  
Yu-Cheng Li ◽  
Jing-Yi Qiao ◽  
Bao-Ying Wang ◽  
Ming Bai ◽  
Ji-Duo Shen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
Protein Expression ◽  
Hepatic Steatosis ◽  
Coenzyme A ◽  
Serum Insulin ◽  
Regulatory Element ◽  
Fatty Acid Synthetase ◽  
Alcoholic Fatty Liver

The present study aimed to evaluate the effects of paeoniflorin on insulin resistance and hepatic steatosis induced by fructose. Male Sprague-Dawley rats were fed 20% fructose drink for eight weeks. The insulin sensitivity, serum lipid profiles, and hepatic lipids contents were measured. The results showed that paeoniflorin significantly decreased serum insulin and glucagon levels, improved insulin sensitivity and serum lipids profiles, and alleviated hepatic steatosis in fructose-fed rats. Moreover, paeoniflorin enhanced the phosphorylation level of AMP-activated protein kinase (AMPK) and protein kinase B (PKB/AKT) and inhibited the phosphorylation of acetyl coenzyme A carboxylase (ACC)1 in liver. Paeoniflorin also increased the hepatic carnitine palmitoyltransferase (CPT)-1 mRNA and protein expression and decreased the mRNA expression of sterol regulatory element-binding protein (SREBP)1c, stearyl coenzyme A decarboxylase (SCD)-1 and fatty acid synthetase (FAS). Furthermore, we found that paeoniflorin significantly increased the heptatic protein expression of tumor suppressor serine/threonine kinase (LKB)1 but not Ca2+/CaM-dependent protein kinase kinase (CaMKK)β. These results suggest that the protective effects of paeoniflorin might be involved in the activation of LKB1/AMPK and insulin signaling, which resulted in the inhibition of lipogenesis, as well as the activation of β-oxidation and glycogenesis, thus ameliorated the insulin resistance and hepatic steatosis. The present study may provide evidence for the beneficial effects of paeoniflorin in the treatment of insulin resistance and non-alcoholic fatty liver.

scholarly journals Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

2021 ◽  
Vol 22 (14) ◽  
pp. 7256
Author(s):  
Vianet Argelia Tello-Flores ◽  
Fredy Omar Beltrán-Anaya ◽  
Marco Antonio Ramírez-Vargas ◽  
Brenda Ely Esteban-Casales ◽  
Napoleón Navarro-Tito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Species ◽  
Necrosis Factor Alpha ◽  
Polypyrimidine Tract Binding Protein ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

Lycopsamine Attenuates Diabetes Mellitus via The Nuclear Factor Kappa B-Induced 5′ Adenosine Monophosphate-Activated Protein Kinase Signal Pathway

2021 ◽  
Vol 20 (1) ◽  
pp. 169-176
Author(s):  
Jingfang Hu ◽  
Jie Jin ◽  
Yan Chen ◽  
Jinyi Wei ◽  
Hanbei Chen
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Protein Kinase ◽  
Nuclear Factor Kappa B ◽  
Adenosine Monophosphate ◽  
Interleukin 10 ◽  
Diabetic Rats ◽  
Nuclear Factor ◽  
Nonesterified Fatty Acids ◽  
Nuclear Factor Kappa

Diabetes mellitus is a metabolic disorder characterized by inflammation, abnormal glycolipid metabolism, insulin resistance, and mitochondrial dysfunction leading to hyperglycemia. The aim of the present investigation was to determine the efficacy of lycopsamine in a rat model of diabetes mellitus to understand its mechanism. Lycopsamine treatment markedly lowered the level of total cholesterol, triglyceride, nonesterified fatty acids, and low-density lipoprotein in diabetic rats. There was also a reduction in interleukin-6, interleukin-10, C-reactive protein, and tumor necrosis factor-α levels. Lycopsamine treatment normalized the metabolism of lipid and glucose, insulin resistance, and body weight of diabetic rats. Findings of immunohistochemical analyses exhibited rise in precipitation of immunocytes in renal cells. Results potentially demonstrated that lycopsamine treatment remarkably reduced the nuclear factor-kappa B level and enhanced the 5′ adenosine monophosphate-activated protein kinase expression. Altogether, administration of lycopsamine suppressed the expression of inflammatory cytokines and attenuated the metabolic symptoms in diabetes mellitus experimental rats.

Abstract 244: The Flavonoids Naringenin and Nobiletin Stimulate the AMPKinase Pathway in Primary Mouse Hepatocytes

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Joshua P Samsoondar ◽  
Lazar A Bojic ◽  
Brian G Sutherland ◽  
Gregory R Steinberg ◽  
Jane Y Edwards ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Hepatic Steatosis ◽  
Dependent Manner ◽  
Ampk Activation ◽  
Metabolic Dysregulation ◽  
Malonyl Coa ◽  
Primary Mouse Hepatocytes ◽  
Primary Mouse ◽  
Mouse Hepatocytes

Dyslipidemia associated with insulin resistance and obesity are core features of the metabolic syndrome and type 2 diabetes, which contribute significantly to atherosclerosis. In mouse models of diet-induced metabolic dysregulation, the citrus flavonoids naringenin and nobiletin prevent obesity, hepatic steatosis, apoB100 overproduction, dyslipidemia, insulin resistance and atherosclerosis. To elucidate the mechanism of action in liver we assessed flavonoid-induced activation of AMP-activated protein kinase (AMPK), the major regulator of cellular energy homeostasis, in primary mouse hepatocytes. Stimulated AMPK activity promotes catabolic, ATP-generating processes such as fatty acid (FA) oxidation while inhibiting anabolic processes such as FA synthesis. In primary C57BL/6 (WT) hepatocytes, naringenin and nobiletin increased phosphorylation (P) of AMPK and its downstream target acetyl-CoA carboxylase (ACC) in a time- and dose-dependent manner. This was associated with decreased apoB100 secretion. Phosphorylation of ACC by AMPK inhibits the formation of malonyl-CoA reducing substrate for FA synthesis in the cytosol while relieving inhibition of mitochondrial FA oxidation by malonyl-CoA. Under insulin resistant conditions stimulated by high glucose media, reduced pAMPK and pACC were reversed by flavonoid treatment in WT hepatocytes, whereas these effects were lost in Ampkβ1-/- hepatocytes. Sterol receptor element binding protein-1c, which stimulates lipogenesis, was also phosphorylated (inhibited) by flavonoid-induced AMPK activation. BAPTA, a calcium chelator or STO609, an inhibitor of Ca2+/calmodulin-dependent protein kinase kinase-beta (CaMKKβ), did not block flavonoid-induced pACC, suggesting that CaMKKβ is not required for AMPK activation by flavonoids. In chow-fed Ldlr-/- mice, acute i.p. injection of nobiletin following a fasting-refeeding protocol, depressed the respiratory exchange ratio indicative of a switch to FA oxidation. Freeze-clamped liver samples from these mice sacrificed 90 min. post injection showed marked induction of pAMPK and pACC. These results suggest that naringenin and nobiletin attenuate hepatic steatosis and metabolic dysregulation, in part, through activation of hepatic AMPK.

scholarly journals Loss of protein kinase Cβ function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance

Hepatology ◽  
2008 ◽  
Vol 49 (5) ◽  
pp. 1525-1536 ◽  
Author(s):  
Wei Huang ◽  
Rishipal Bansode ◽  
Madhu Mehta ◽  
Kamal D. Mehta
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Hepatic Steatosis ◽  
Diet Induced Obesity
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