Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice

doi:10.1371/journal.pone.0042115

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	Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice
	Zeng, Xiao-Yi 1,2; Wang, Yi-Ping1,2 ; Cantley, James 4; Iseli, Tristan J.4; Molero, Juan Carlos 1,2; Hegarty, Bronwyn D.4; Kraegen, Edward W.4; Ye, Yang3 ; Ye, Ji-Ming 1,2,3,4
刊名	PLOS ONE
	2012-07-30
卷号	7 期号:7
ISSN号	1932-6203
DOI	10.1371/journal.pone.0042115
文献子类	Article
英文摘要	The present study investigated the chronic efficacy of oleanolic acid (OA), a triterpenoid selected from our recent screening, on hyperglycemia in type-2 diabetic mice. C57BL/6J mice were fed a high-fat diet followed by low doses of streptozotocin to generate a type-2 diabetic model. OA (100 mg/kg/day) was administered orally for 2 weeks with its effects monitored for 6 weeks. High-fat feeding and streptozotocin generated a steady hyperglycemia (21.2 +/- 1.1 mM) but OA administration reversed the hyperglycemia by similar to 60%. Interestingly, after the cessation of OA administration, the reversed hyperglycemia was sustained for the entire post-treatment period of the study (4 weeks) despite the reoccurrence of dyslipidemia. Examination of insulin secretion and pancreas morphology did not indicate improved beta-cell function as a likely mechanism. Urine glucose loss was decreased with substantial improvement of diabetic nephropathy after the OA treatment. Pair-feeding the OA-treated mice to an untreated group ruled out food intake as a main factor attributable for this sustained reduction in hyperglycemia. Studies with the use of glucose tracers revealed no increase in glucose influx into muscle, adipose tissue or liver in the OA-treated mice. Finally, we analyzed key regulators of gluconeogenesis in the liver and found significant increases in the phosphorylation of both Akt and FoxO1 after treatment with OA. Importantly, these increases were significantly correlated with a down-regulation of glucose-6-phosphatase expression. Our findings suggest triterpenoids are a potential source of new efficacious drugs for sustained control of hyperglycemia. The liver appears to be a major site of action, possibly by the suppression of hepatic glucose production via the Akt/FoxO1 axis.
资助项目	National Health and Medical Research Council[NHMRC Project Grant] ; International Scientific Linkage Program Grant of Australia[CH 080212]
WOS关键词	INDUCED INSULIN-RESISTANCE ; FAT-FED RATS ; METABOLIC SYNDROME ; GLUCOSE-TOLERANCE ; GLYCEMIC CONTROL ; SMALL-MOLECULE ; URSOLIC ACID ; BETA-CELLS ; OBESITY ; DIET
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000306950900069
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278009]
专题	天然药物化学研究室
通讯作者	Zeng, Xiao-Yi
作者单位	1.RMIT Univ, Sch Hlth Sci, Melbourne, Vic, Australia; 2.RMIT Univ, Hlth Innovat Res Inst, Melbourne, Vic, Australia; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China 4.Garvan Inst Med Res, Diabet & Obes Program, Sydney, NSW, Australia;
推荐引用方式 GB/T 7714	Zeng, Xiao-Yi,Wang, Yi-Ping,Cantley, James,et al. Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice[J]. PLOS ONE,2012,7(7).
APA	Zeng, Xiao-Yi.,Wang, Yi-Ping.,Cantley, James.,Iseli, Tristan J..,Molero, Juan Carlos.,...&Ye, Ji-Ming.(2012).Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice.PLOS ONE,7(7).
MLA	Zeng, Xiao-Yi,et al."Oleanolic Acid Reduces Hyperglycemia beyond Treatment Period with Akt/FoxO1-Induced Suppression of Hepatic Gluconeogenesis in Type-2 Diabetic Mice".PLOS ONE 7.7(2012).