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Can Liu Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Mian Zhang Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Meng-yue Hu Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Hai-fang Guo Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Jia Li Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Yun-li Yu Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Shi Jin Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Xin-ting Wang Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Li Liu Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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Xiao-dong Liu Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China

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, it is noteworthy that local high concentration of ginsenosides in intestine may interact with intestinal epithelium, where numerous endocrine cells are located. Glucagon-like peptide-1 (GLP1), secreted by enteroendocrine L-cells, is one of the most

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Hongbin Liu Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Yunshan Hu Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Richard W Simpson Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Anthony E Dear Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Eastern Clinical Research Unit, Department of Diabetes and Endocrinology, Biotechnology Division, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Introduction Glucagon-like peptide-1 (GLP-1), an incretin first identified in 1984, has been proposed as a potential candidate target for therapy in the treatment of type 2 diabetes ( Nauck et al . 1993 , Edwards 2005 ). GLP-1, the product of the

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Patrice D Cani Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
Unit of Animal Biology, Université catholique de Louvain, Brussels, Belgium

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Catherine A Daubioul Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
Unit of Animal Biology, Université catholique de Louvain, Brussels, Belgium

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Brigitte Reusens Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
Unit of Animal Biology, Université catholique de Louvain, Brussels, Belgium

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Claude Remacle Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
Unit of Animal Biology, Université catholique de Louvain, Brussels, Belgium

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Grégory Catillon Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
Unit of Animal Biology, Université catholique de Louvain, Brussels, Belgium

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Nathalie M Delzenne Unit of Pharmacokinetics, Metabolism, Nutrition and Toxicology, Université catholique de Louvain, Brussels, Belgium
Unit of Animal Biology, Université catholique de Louvain, Brussels, Belgium

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( Reimer & McBurney 1996 , Cani et al. 2004 ). In the intestine, the post-translational modification of the proglucagon gene by prohormone convertase 1 (PC1) leads to the production of glucagon-like peptide-1(7–36) amide (GLP-1(7–36) amide) which, among

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Hongbin Liu Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Anthony E Dear Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Lotte B Knudsen Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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Richard W Simpson Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia
Australian Centre for Blood Diseases, Eastern Clinical Research Unit, Novo Nordisk A/S, Department of Diabetes and Endocrinology, Monash University, 6th Floor Burnett Tower, 89 Commercial Road, Prahran 3181, Melbourne, Victoria, Australia

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protected from the development of biochemical abnormalities associated with endothelial cell dysfunction and development of atherosclerosis ( Eitzman et al . 2000 , Mao et al . 2004 ). Liraglutide, an acylated glucagon-like peptide-1 (GLP-1) analogue, has

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Neville H McClenaghan School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Chemicon International Inc., 28820 Single Oak Drive, Temecula, California 92590, USA

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Peter R Flatt School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Chemicon International Inc., 28820 Single Oak Drive, Temecula, California 92590, USA

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Andrew J Ball School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Chemicon International Inc., 28820 Single Oak Drive, Temecula, California 92590, USA

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-cell desensitisation compared with sulphonylureas may occur following prolonged exposure to nateglinide ( Ball et al. 2004 b ). In vivo , insulin secretion can be stimulated by glucagon-like peptide-1 (GLP-1), a hormone of the enteroinsular axis, released

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L Bai Diabetes Transplant Unit, Prince of Wales Hospital and The University of New South Wales, Sydney, Australia

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G Meredith Diabetes Transplant Unit, Prince of Wales Hospital and The University of New South Wales, Sydney, Australia

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B E Tuch Diabetes Transplant Unit, Prince of Wales Hospital and The University of New South Wales, Sydney, Australia

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Introduction Glucagon-like peptide-1 (GLP-1) is a peptide secreted from the gut in response to food. It acts directly on β cells, enhancing the effect of glucose in stimulating insulin secretion from these cells. When administered to

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Hong Lan Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Galya Vassileva Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Aaron Corona Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Li Liu Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Hana Baker Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Andrei Golovko Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Susan J Abbondanzo Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Weiwen Hu Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Shijun Yang Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Yun Ning Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Robert A Del Vecchio Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Frederique Poulet Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Maureen Laverty Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Eric L Gustafson Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Joseph A Hedrick Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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Timothy J Kowalski Cardiovascular and Metabolic Disease Research, Drug Safety,, Departments of

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fall into two major categories: drugs that improve insulin sensitivity, and those that increase insulin secretion from β-cells. Agents that enhance insulin secretion in a glucose-dependent manner, such as glucagon-like peptide-1 (GLP-1) mimetics (e

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B D Green School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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N Irwin School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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V A Gault School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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C J Bailey School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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F P M O’Harte School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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P R Flatt School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
School of Pharmaceutical and Biological Sciences, Aston University, Birmingham, UK

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Introduction The incretin hormone glucagon-like peptide-1 (GLP-1) has potent insulinotropic effects on pancreatic β-cells, and further promotes glucose lowering by enhancing glucose uptake and glyconeogenesis in peripheral tissues

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Patricia Vázquez Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain

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Isabel Roncero Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain

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Enrique Blázquez Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain

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Elvira Alvarez Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain

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Introduction Glucagon-like peptide-1(7–36)amide (GLP-1) is an intestinal peptide synthesised in L-cells. It is also produced in the brain ( Jin et al. 1988 , Kreymann et al. 1989 ), where it exerts some effects on

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Thomas H Claus Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Clark Q Pan Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Joanne M Buxton Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Ling Yang Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Jennifer C Reynolds Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Nicole Barucci Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Michael Burns Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Astrid A Ortiz Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Steve Roczniak Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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James N Livingston Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Kevin B Clairmont Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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James P Whelan Bayer HealthCare, Pharmaceuticals, Department of Metabolic Disease Research, 400 Morgan Lane, West Haven, Connecticut 06516 USA
Bayer HealthCare, Biotechnology, 800 Dwight Way, Berkeley, California 94701, USA

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Introduction Glucagon-like peptide-1 (GLP-1) is a potent endogenous modulator of insulin secretion that is released by the L-cells in the crypts of the jejunum and ileum in response to a meal ( Kieffer & Habener 1999 ). Its function

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