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Horm Metab Res 2010; 42(13): 930-935
DOI: 10.1055/s-0030-1265219
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Amelioration of Insulin Resistance by Scopoletin in High-Glucose-Induced, Insulin-Resistant HepG2 Cells

W. Y. Zhang1 , 2 , J.-J. Lee1 , 3 , Y. Kim1 , I.-S. Kim1 , J.-S. Park3 , 4 , 5 , C.-S. Myung1 , 3 , 5
  • 1Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Republic of Korea
  • 2Present address: Department of Chemical Biology, Xiamen University College of Chemistry and Chemical Engineering, Xiamen 361005, P. R. China
  • 3Institute of Drug Research & Development, Chungnam National University, Daejeon 305-764, Republic of Korea
  • 4Department of Physical Pharmacy, Chungnam National University College of Pharmacy, Daejeon 305-764, Republic of Korea
  • 5Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 305-764, Republic of Korea
Further Information

Publication History

received 05.05.2010

accepted 24.08.2010

Publication Date:
30 September 2010 (online)

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Abstract

Insulin resistance plays an important role in the development of type 2 diabetes mellitus. Scopoletin, a phenolic coumarin, is reported to regulate hyperglycemia and diabetes. To examine its effect on insulin resistance, we treated high-glucose-induced, insulin-resistant HepG2 cells with scopoletin and measured phosphatidylinositol 3-kinase (PI3 K)-linked protein kinase B (Akt/PKB) phosphorylation. Scopoletin significantly stimulated the reactivation of insulin-mediated Akt/PKB phosphorylation. This effect was blocked by LY294002, a specific PI3 K inhibitor. The ability of scopoletin to activate insulin-mediated Akt/PKB was greater than that of rosiglitazone, a thiazolidinedione, and scopoletin was less adipogenic than rosiglitazone, as shown by the extent of lipid accumulation in differentiated adipocytes. Scopoletin increased the gene expression of both peroxisome proliferator-activated receptor γ2 (PPARγ2), a target receptor for rosiglitazone, and adipocyte-specific fatty acid binding protein, but not to the level induced by rosiglitazone. However, the PPARγ2 protein level was increased equally by rosiglitazone and scopoletin in differentiated adipocytes. Our results suggest that scopoletin can ameliorate insulin resistance in part by upregulating PPARγ2 expression. With its lower adipogenic property, scopoletin may be a useful candidate for managing metabolic disorders, including type 2 diabetes mellitus.

Key words

Akt/PKB - insulin resistance - PPARγ2 - scopoletin - type 2 diabetes mellitus

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Correspondence

Dr. C-S. Myung

Department of Pharmacology

Chungnam National University

College of Pharmacy

220 Geung-dong, Yuseong-gu

Daejeon 305-764

Republic of Korea

Phone: +82/42/821 5923

Fax: +82/42/821 8900

Email: cm8r@cnu.ac.kr

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