Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase

Hwang, Soo Min; Yang, Byung-Keun; Lee, Jai-Youl; Kim, Jeong‐Han; Kim, Byung-Hong; Suh, Ki-Hyoung; Kim, Dae-Yong; Kim, Moon Sung; Song, Hebok; Park, Byeoung-Soo; Huh, Tae‐Lin

doi:10.1016/j.bbrc.2008.04.061

Cited by 26 publications

(15 citation statements)

References 32 publications

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“…L6 cells (American Type Culture Collection, Manassas, VA) were maintained in a-minimum Eagle's medium (Invitrogen, Carlsbad, CA) supplemented with 10% (v/v) fetal bovine serum, 100 U/ml penicillin, and 100 mg/ml streptomycin in a humidified 5% CO 2 atmosphere at 37°C. Cells were allowed to differentiate into myotubes as reported previously (Hwang et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

“…L6 myotubes and tissue samples were isolated and processed as described previously (Hwang et al, 2008). The polyvinylidene difluoride membranes (Calbiochem) were probed with liver kinase B1 (LKB1), AMPK, pAMPK, ACC (acetyl-CoA carboxylase), pACC, protein kinase-like ER resident kinase (PERK), pPERK, inositol-requiring kinase-1 (IRE1), pIRE1, c-Jun NH 2 -terminal kinase (JNK), pJNK, mTOR, pmTOR, S6K, pS6K, 4E binding protein (4E-BP), p4E-BP, Akt, and pAkt (all from Cell Signaling Technology, Beverly, MA), and b-tubulin (Santa Cruz Biotechnology, Santa Cruz, CA), and then developed using an enhanced chemiluminescence Western blot detection kit (Amersham Bioscience, Piscataway, NJ).…”

Section: Methodsmentioning

confidence: 99%

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Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes

et al. 2013

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Low molecular weight fucoidan (LMWF) is widely used to treat metabolic disorders, but its physiologic effects have not been well determined. In the present study, we investigated the metabolic effects of LMWF in obese diabetic mice (leptin receptor-deficient db/db mice) and the underlying molecular mechanisms involved in endoplasmic reticulum (ER) stressresponsive L6 myotubes. The effect of LMWF-mediated AMP-activated protein kinase (AMPK) activation on insulin resistance via regulation of the ER stress-dependent pathway was examined in vitro and in vivo. In db/db mice, LMWF markedly reduced serum glucose, triglyceride, cholesterol, and low-density lipoprotein levels, and gradually reduced body weights by reducing lipid parameters. Furthermore, it effectively ameliorated glucose homeostasis by elevating glucose tolerance. In addition, the phosphorylation levels of AMPK and Akt were markedly reduced by ER stressor, and subsequently, glucose uptake and fatty acid oxidation were also reduced. However, these adverse effects of ER stress were significantly ameliorated by LMWF. Finally, in L6 myotubes, LMWF markedly reduced the ER stress-induced upregulation of the mammalian target of rapamycin-p70S61 kinase network and subsequently improved the action of insulin via AMPK stimulation. Our findings suggest that AMPK activation by LMWF could prevent metabolic diseases by controlling the ER stress-dependent pathway and that this beneficial effect of LMWF provides a potential therapeutic strategy for ameliorating ER stress-mediated metabolic dysfunctions.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes

et al. 2013

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“…For example, capsaicinoids, extracted from hot peppers, are shown to induce fatty acid oxidation and decrease body fat accumulation in diabetic mice. The synthetic structural ester isomer isodihydrocapsiate activates LKB1 both in vitro and in vivo ( 262 ). In L6 myotubes, these substances increased glucose uptake and reduced blood glucose in the myocytes of diabetic mice.…”

Section: Long Chain-fatty Acids Pufa and Fatty Acid Analogsmentioning

confidence: 98%

AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

Srivastava

Pinkosky

Filippov

et al. 2012

Journal of Lipid Research

256

179

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This article is available online at http://www.jlr.org termed as metabolic syndrome (MetS) ( 1 ), characterized by a clustering of major risk factors for developing cardiovascular disease. Obesity, representing derangement in energy balances, is tightly linked with the development of type-2 diabetes through its ability to engender insulin resistance, leading to glucose intolerance and development of type-2 diabetes and dyslipidemia. Thus, insulin resistance The pathophysiology of diabetes and obesity is a very complex process involving many pathways. Deregulation of these pathways gives rise to metabolic abnormalities

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“…For example, capsaicinoids, a group of the natural compounds extracted from hot peppers, have been reported to promote fatty acid oxidation and decrease body fat accumulation in diabetic mice. The synthetic structural ester isomer isodihydrocapsiate activates LKB1 both in vitro and in vivo [152]. This substance also increases glucose uptake in L6 myotubes and when administered orally to diabetic mice it substantially reduces blood glucose.…”

Section: Capsaicinoidsmentioning

confidence: 99%

Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations

Babai²,

2009

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■ AbstractIn view of the epidemic nature of type 2 diabetes and the substantial rate of failure of current oral antidiabetic drugs the quest for new therapeutics is intensive. The adenosine monophosphate-activated protein kinase (AMPK) is an important regulatory protein for cellular energy balance and is considered a master switch of glucose and lipid metabolism in various organs, especially in skeletal muscle and liver. In skeletal muscles, AMPK stimulates glucose transport and fatty acid oxidation. In the liver, it augments fatty acid oxidation and decreases glucose output, cholesterol and triglyceride synthesis. These metabolic effects induced by AMPK are associated with lowering blood glucose levels in hyperglycemic individuals. Two classes of oral antihyperglycemic drugs (biguanidines and thiazolidinediones) have been shown to exert some of their therapeutic effects by directly or indirectly activating AMPK. However, side effects and an acquired resistance to these drugs emphasize the need for the development of novel and efficacious AMPK activators. We have recently discovered a new class of hydrophobic Dxylose derivatives that activates AMPK in skeletal muscles in a non insulin-dependent manner. One of these derivatives (2,4;3,5-dibenzylidene-D-xylose-diethyl-dithioacetal) stimulates the rate of hexose transport in skeletal muscle cells by increasing the abundance of glucose transporter-4 (GLUT-4) in the plasma membrane through activation of AMPK. This compound reduces blood glucose levels in diabetic mice and therefore offers a novel strategy of therapeutic intervention strategy in type 2 diabetes. The present review describes various classes of chemically-related compounds that activate AMPK by direct or indirect interactions and discusses their potential for candidate antihyperglycemic drug development.

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Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase

Cited by 26 publications

References 32 publications

Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes

Low Molecular Weight Fucoidan Improves Endoplasmic Reticulum Stress-Reduced Insulin Sensitivity through AMP-Activated Protein Kinase Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes

AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations

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