Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats

被引：88

作者：

Gong, Jing ^{[1
]}

Hu, Meilin ^{[1
]}

Huang, Zhaoyi ^{[2
]}

Fang, Ke ^{[1
]}

Wang, Dingkun ^{[2
]}

Chen, Qingjie ^{[3
]}

Li, Jingbin ^{[2
]}

Yang, Desen ^{[1
,4
]}

Zou, Xin ^{[1
]}

Xu, Lijun ^{[1
]}

Wang, Kaifu ^{[1
]}

Dong, Hui ^{[1
]}

Lu, Fuer ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Inst Integrated Tradit Chinese & Western Med, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China

[2] Huazhong Univ Sci & Technol, Dept Integrated Tradit Chinese & Western Med, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China

[3] Huazhong Univ Sci & Technol, Dept Biochem & Mol Biol, Tongji Med Coll, Wuhan, Peoples R China

[4] Hubei Univ Tradit Chinese Med, Dept Pharm, Wuhan, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

berberine; diabetes; intestinal mucosal barrier; gut immune system; gut-derived hormones; GUT MICROBIOTA; INSULIN-RESISTANCE; CROSS-TALK; METFORMIN; OBESITY; GLUCOSE; INFLAMMATION; KINASE; GLP-1;

D O I：

10.3389/fphar.2017.00042

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-kappa B signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.

引用

页数：12

共 42 条

[11] Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats (vol 21, pg 506, 2015) [J].

Duca, Frank A. ;

Cote, Clemence D. ;

Rasmussen, Brittany A. ;

Zadeh-Tahmasebi, Melika ;

Rutter, Guy A. ;

Filippi, Beatrice M. ;

Lam, Tony K. T. .

NATURE MEDICINE, 2015, 21 (05) :506-U130

[12] Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity [J].

Everard, Amandine ;

Belzer, Clara ;

Geurts, Lucie ;

Ouwerkerk, Janneke P. ;

Druart, Celine ;

Bindels, Laure B. ;

Guiot, Yves ;

Derrien, Muriel ;

Muccioli, Giulio G. ;

Delzenne, Nathalie M. ;

de Vos, Willem M. ;

Cani, Patrice D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (22) :9066-9071

[13] Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota [J].

Forslund, Kristoffer ;

Hildebrand, Falk ;

Nielsen, Trine ;

Falony, Gwen ;

Le Chatelier, Emmanuelle ;

Sunagawa, Shinichi ;

Prifti, Edi ;

Vieira-Silva, Sara ;

Gudmundsdottir, Valborg ;

Pedersen, Helle Krogh ;

Arumugam, Manimozhiyan ;

Kristiansen, Karsten ;

Voigt, Anita Yvonne ;

Vestergaard, Henrik ;

Hercog, Rajna ;

Costea, Paul Igor ;

Kultima, Jens Roat ;

Li, Junhua ;

Jorgensen, Torben ;

Levenez, Florence ;

Dore, Joel ;

Nielsen, H. Bjorn ;

Brunak, Soren ;

Raes, Jeroen ;

Hansen, Torben ;

Wang, Jun ;

Ehrlich, S. Dusko ;

Bork, Peer ;

Pedersen, Oluf .

NATURE, 2015, 528 (7581) :262-+

[14] Acquisition of a multifunctional IgA+ plasma cell phenotype in the gut [J].

Fritz, Joerg H. ;

Rojas, Olga Lucia ;

Simard, Nathalie ;

McCarthy, Douglas D. ;

Hapfelmeier, Siegfried ;

Rubino, Stephen ;

Robertson, Susan J. ;

Larijani, Mani ;

Gosselin, Jean ;

Ivanov, Ivaylo I. ;

Martin, Alberto ;

Casellas, Rafael ;

Philpott, Dana J. ;

Girardin, Stephen E. ;

McCoy, Kathy D. ;

Macpherson, Andrew J. ;

Paige, Christopher J. ;

Gommerman, Jennifer L. .

NATURE, 2012, 481 (7380) :199-+

[15] The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease [J].

Garidou, Lucile ;

Pomie, Celine ;

Klopp, Pascale ;

Waget, Aurelie ;

Charpentier, Julie ;

Aloulou, Meryem ;

Giry, Anais ;

Serino, Matteo ;

Stenman, Lotta ;

Lahtinen, Sampo ;

Dray, Cedric ;

Iacovoni, Jason S. ;

Courtney, Michael ;

Collet, Xavier ;

Amar, Jacques ;

Servant, Florence ;

Lelouvier, Benjamin ;

Valet, Philippe ;

Eberl, Gerard ;

Fazilleau, Nicolas ;

Douin-Echinard, Victorine ;

Heymes, Christophe ;

Burcelin, Remy .

CELL METABOLISM, 2015, 22 (01) :100-112

[16] Enteropathy precedes type 1 diabetes in the BB rat [J].

Graham, S ;

Courtois, P ;

Malaisse, WJ ;

Rozing, J ;

Scott, FW ;

Mowat, AM .

GUT, 2004, 53 (10) :1437-1444

[17] The human milk oligosaccharide 2′-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation [J].

He, YingYing ;

Liu, ShuBai ;

Kling, David E. ;

Leone, Serena ;

Lawlor, Nathan T. ;

Huang, Yi ;

Feinberg, Samuel B. ;

Hill, David R. ;

Newburg, David S. .

GUT, 2016, 65 (01) :33-+

[18] Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying [J].

Janssen, Sara ;

Laermans, Jorien ;

Verhulst, Pieter-Jan ;

Thijs, Theo ;

Tack, Jan ;

Depoortere, Inge .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (05) :2094-2099

[19]

Leng SH, 2004, ACTA PHARMACOL SIN, V25, P496

[20] Effects of dietary fat on appetite and energy intake in health and obesity - Oral and gastrointestinal sensory contributions [J].

Little, Tanya J. ;

Feinle-Bisset, Christine .

PHYSIOLOGY & BEHAVIOR, 2011, 104 (04) :613-620

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