title: Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc-ESI-Hdms.
abstract: The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.|Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, No. 132, Tianmushan Road, Hangzhou, 310007, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.
authors.forename: Yuan-Xiao
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Dai
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Tong
authors.affiliation: Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, No. 132, Tianmushan Road, Hangzhou, 310007, China.|Department of Chemistry, Zhejiang University, Xixi Campus, No. 148, Tianmushan Road, Hangzhou, 310028, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shou
authors.affiliation: Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, China.
authors.forename: Changyu
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D001599:Berberine / Q000737:chemistry* / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D001599:Berberine
keywords: UPLC-ESI-HDMS; Zucker diabetic fatty rats; berberine; metabolomics; pattern recognition approach; type 2 diabetes