Peroxisome Proliferators‐Activated Receptor (PPAR) Modulators and Metabolic Disorders

Cho, Min-Chul; Lee, Kyung Ho; Paik, Sang‐Gi; Yoon, Do‐Young

doi:10.1155/2008/679137

Cited by 74 publications

(66 citation statements)

References 121 publications

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“…PPAR ␥ is expressed at high levels in adipose tissue [9] , where it plays an important role in the regulation of genes involved in adipocyte differentiation, lipid storage, glucose metabolism, and insulin sensitivity [30,31] . Differentiated adipocytes are required for expression of proteins involved in hormonal action and signaling, lipogenesis and lipolysis, fatty acid binding, and insulinsensitive glucose transport [4,32] .…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Glucose Uptake and Improvement of Insulin Resistance by Aromadendrin

et al. 2011

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Agents that stimulate glucose uptake and improve insulin resistance may be useful in the management of type 2 diabetes mellitus (DM). Thus, the aims of this study were to assess the effects of aromadendrin, a flavonoid from Gleditsia sinensis Lam., on stimulation of glucose uptake and improvement of insulin resistance and to characterize the molecular mechanisms underlying these activities. Insulin-stimulated glucose uptake was measured in HepG2 cells and in differentiated 3T3-L1 adipocytes using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent D-glucose analog. Expression of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) and adipocyte-specific fatty acid binding protein (aP2) mRNAs and the PPARγ2 protein was analyzed in adipocytes using RT-PCR and immunoblotting, respectively. Insulin-stimulated protein kinase B (Akt/PKB) phosphorylation was measured in high glucose-induced, insulin-resistant HepG2 cells. Similar to 30 µmol/l rosiglitazone, treatment with 30 µmol/l aromadendrin significantly stimulated insulin-sensitive glucose uptake in both HepG2 cells and 3T3-L1 adipocytes. Aromadendrin treatment also enhanced adipogenesis and caused increases in the expression of PPARγ2 and aP2 mRNAs and the PPARγ2 protein in differentiated 3T3-L1 adipocytes. In high glucose-induced, insulin-resistant HepG2 cells, aromadendrin reversed the inhibition of Akt/PKB phosphorylation in response to insulin, which could be abrogated by pretreatment with LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Aromadendrin treatment induced adipogenesis by increases in PPARγ2 expression, resulting in stimulation of glucose uptake and ameliorated insulin resistance. These findings suggest that aromadendrin may represent a potential therapeutic candidate for the management of type 2 DM.

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Section: Discussionmentioning

confidence: 99%

Stimulation of Glucose Uptake and Improvement of Insulin Resistance by Aromadendrin

et al. 2011

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“…PPARg2, selectively expressed in adipocytes, induces the expression of genes (for example, aP2) necessary for the generation and maintenance of the adipogenic phenotype as well as glucose and lipid metabolism. 25,26) Since PPARg2 exerts the effects on insulin sensitivity and glucose homeostasis, 27) and it is required for adipocyte differentiation, 28) the increase in its expression may manage the level of blood glucose by increasing glucose uptake into mature adipocytes. In a previous study, sakuranetin was revealed to significantly induce adipogenesis, increase insulin-stimulated glucose uptake and improve PPARg mRNA expression, but fail to exhibit PPARg ligand activity even at high doses (100 mM) in luciferase reporter assay.…”

Section: Discussionmentioning

confidence: 99%

7-O-Methylaromadendrin Stimulates Glucose Uptake and Improves Insulin Resistance in Vitro

Zhang

Lee

Kim

et al. 2010

Biological & Pharmaceutical Bulletin

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The much more common condition of diabetes mellitus (DM) is type 2 DM, which represents 90 to 95% of all diagnosed cases of diabetes.1) Insulin resistance, a specific feature of type 2 DM, is the condition whereby major organs such as muscle and liver become resistant to the action of the hormone, leading to increased glucose output from the liver and reduced uptake and metabolism of glucose by other organs. 2)Studies on the molecular basis of insulin resistance have focused on the peroxisome proliferator-activated receptor g (PPARg). PPARg plays an important role in the regulation of genes involved in adipocyte differentiation, lipid storage, glucose metabolism 3) and insulin signal transduction. 4) In this regard, PPARg is a target for the treatment of insulin resistance as rosiglitazone, an anti-diabetic drug, does.Insulin binding to its receptor induces activation of a complex network of downstream molecules, including phosphatidylinositol 3-kinase (PI3K) and the serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB).5,6) Activation of Akt/PKB stimulates membrane translocation of the glucose transporter, GLUT4, 7) leading to enhanced glucose uptake. Thus, Akt/PKB activation is a prerequisite for glucose uptake.Adenosine 5Ј-monophosphate-activated protein kinase (AMPK) acts as an intracellular energy sensor. Increased recruitment of the AMPK signaling system may be effective in correcting insulin resistance. 8) Activation of AMPK acutely stimulates glucose uptake via both GLUT1 and GLUT4, and enhances the long-term expression of GLUT4. 9) Thus, AMPK is responsible for mediating the stimulation of glucose uptake.The whole plant of Inula viscosa L. was traditionally used in folk medicine for treating DM.10-12) Previous investigations revealed the presence of a series of flavonoids in the whole plant including quercetin, apigenin, naringenin, sakuranetin, and aromadendrin. 13,14) Some of the flavonoids were reported to either improve or inhibit insulin-stimulated glucose uptake in adipocytes. [15][16][17] For instance, sakuranetin was revealed to enhance insulin-stimulated glucose uptake in adipocytes, 15) while apigenin suppressed. 17) Quercetin was reported with somewhat conflict in regulating insulin-stimulated glucose uptake.17,18) 7-O-Methylaromadendrin (7-O-MA) is also one of flavonoids isolated from I. viscosa. The preliminary data using our screening system indicated that 7-O-MA showed significant activities on stimulating insulininduced glucose uptake into both HepG2 cells and differentiated 3T3-L1 adipocytes. Therefore, the specific aim of this study was to investigate the ability of 7-O-MA to improve diabetic conditions and the possible molecular basis. Our results observed that 7-O-MA increased expression of PPARg2 and adipocyte-specific fatty acid binding protein The stimulation of glucose uptake into peripheral tissues is an important mechanism for the removal of glucose in blood and for the management of diabetes mellitus ( Key words 7-O-methylaromadendrin; glucose uptake; AMP-activated pr...

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“…3b) (Cho et al, 2008;Musri et al, 2007). The addition of troglitazone induces the exchange of suppressive NCoR/SMRT complexes through causing the expression of PPARγ coactivator 1α (PGC-1α) (Guan et al, 2005).…”

Section: Regulation Of Pparγ By Ligandsmentioning

confidence: 99%

Epigenetic regulation of adipocyte differentiation and adipogenesis

Xiao

Wang

et al. 2010

J. Zhejiang Univ. Sci. B

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Abstract:It is generally agreed that adipocytes originate from mesenchymal stem cells in what can be divided into two processes: determination and differentiation. In the past decade, many factors associated with epigenetic signals have been proved to be pivotal for the appropriate timing of adipogenesis progression. A large number of coregulators at critical gene promoters set up specific patterns of DNA methylation, histone acetylation and methylation, and nucleosome rearrangement, that act as an epigenetic code to modulate the correct progress of adipocyte differentiation and adipogenesis during adipogenesis. In this review, we focus on the functions and roles of epigenetic processes in preadipocyte differentiation and adipogenesis.

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Peroxisome Proliferators‐Activated Receptor (PPAR) Modulators and Metabolic Disorders

Cited by 74 publications

References 121 publications

Stimulation of Glucose Uptake and Improvement of Insulin Resistance by Aromadendrin

Stimulation of Glucose Uptake and Improvement of Insulin Resistance by Aromadendrin

7-O-Methylaromadendrin Stimulates Glucose Uptake and Improves Insulin Resistance in Vitro

Epigenetic regulation of adipocyte differentiation and adipogenesis

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