PMID- 20566415 OWN - NLM STAT- MEDLINE DCOM- 20110131 LR - 20220316 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 641 IP - 2-3 DP - 2010 Sep 1 TI - Antiproliferation of cardamonin is involved in mTOR on aortic smooth muscle cells in high fructose-induced insulin resistance rats. PG - 179-86 LID - 10.1016/j.ejphar.2010.05.024 [doi] AB - The objective of this study was to determine possible effects and potential mechanisms of cardamonin on improving insulin resistance and vascular proliferative lesions in the rat's model system. Fed with 60% fructose-enriched diet for 12 weeks, male Sprague-Dawley (SD) rats developed insulin resistance and hyperinsulinemia. They also showed excessive proliferation of the vascular smooth muscle cells (VSMCs) and activation of the mammalian target of rapamycin (mTOR)/translation control proteins p70 ribosomal S6 kinase (P70S6K1)/eukaryotic initiation factor 4E binding protein 1 (4E-BP1) signaling in the rat thoracic aorta. From weeks 9-12, cardamonin was injected into the peritoneal cavity once daily. Under the detection of microscopy and electron microscopy, cardamonin improved hyperinsulinemia and inhibited proliferation of VSMCs in the thoracic aorta of rats in a dose-dependent manner. By the Real-Time RT-PCR, mRNA expression of mTOR, P70S6K1 and 4E-BP1 was significantly reduced in cardamonin treated rats. Similarly, protein over-expression of mTOR and p-P70S6K1 was obviously inhibited by immunohistochemical analyses. These findings suggest that cardamonin may play a role in ameliorating insulin resistance and smooth muscle hyperplasia of major vessels in fructose-induced rats, possibly via a mechanism that involves the modulation of insulin/mTOR signaling. CI - Copyright (c) 2010 Elsevier B.V. All rights reserved. FAU - Liao, Qin AU - Liao Q AD - Department of Pharmacy, Fuzhou General Hospital of Nanjing Military Command, Fujian Fuzhou, China. FAU - Shi, Dao-Hua AU - Shi DH FAU - Zheng, Wei AU - Zheng W FAU - Xu, Xiang-Jin AU - Xu XJ FAU - Yu, Ying-Hao AU - Yu YH LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100604 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Carrier Proteins) RN - 0 (Chalcones) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 30237-26-4 (Fructose) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - H8KP1OJ8JX (cardamonin) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Aorta, Thoracic/cytology/metabolism/ultrastructure MH - Carrier Proteins/metabolism MH - Cell Proliferation/*drug effects MH - Chalcones/chemistry/*pharmacology MH - Dose-Response Relationship, Drug MH - Fructose/*pharmacology MH - Hyperinsulinism/drug therapy MH - Hypoglycemic Agents/pharmacology MH - Insulin/metabolism/pharmacology MH - Insulin Resistance/*physiology MH - Male MH - Mammals MH - Molecular Structure MH - Muscle, Smooth, Vascular/pathology/ultrastructure MH - Myocytes, Smooth Muscle/*metabolism MH - Random Allocation MH - Rats MH - Rats, Sprague-Dawley MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction/drug effects/physiology MH - Sirolimus/pharmacology MH - TOR Serine-Threonine Kinases/*metabolism EDAT- 2010/06/23 06:00 MHDA- 2011/02/01 06:00 CRDT- 2010/06/23 06:00 PHST- 2009/09/07 00:00 [received] PHST- 2010/04/17 00:00 [revised] PHST- 2010/05/23 00:00 [accepted] PHST- 2010/06/23 06:00 [entrez] PHST- 2010/06/23 06:00 [pubmed] PHST- 2011/02/01 06:00 [medline] AID - S0014-2999(10)00474-7 [pii] AID - 10.1016/j.ejphar.2010.05.024 [doi] PST - ppublish SO - Eur J Pharmacol. 2010 Sep 1;641(2-3):179-86. doi: 10.1016/j.ejphar.2010.05.024. Epub 2010 Jun 4.