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Linda Ahlkvist, Bilal Omar, Anders Valeur, Keld Fosgerau, and Bo Ahrén

tolerance test (IVGTT) was performed where the mice were injected with glucose (0.35 g/kg, Sigma) in a tail vein with or without glucagon-like peptide 1 (GLP1) (3 nmol/kg, Sigma). Blood samples were collected at different time points into heparinized tubes

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Jia Fang Wang and David J Hill

endothelial cell CD31/PECAM-1 were obtained from Dako Corporation, Santa Barbara, CA, USA, and rabbit anti-human α amylase from Sigma Chemical Co. Rabbit anti-rat PDX-1 was provided by Dr C Wright, Vanderbilt University. Glucagon-like polypeptide 1 (GLP-1) and

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BD Green, MH Mooney, VA Gault, N Irwin, CJ Bailey, P Harriott, B Greer, FP O'Harte, and PR Flatt

Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC(50) values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC(50) 0.37 nM). Similarly, both analogues stimulated cAMP production with EC(50) values of 16.3 and 27 nM respectively compared with GLP-1 (EC(50) 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P<0.05 to P<0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes.

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Tao Xie, Min Chen, and Lee S Weinstein

. 2003 ). In addition, type 2 diabetics also have increased glucagon (GCG) secretion from pancreatic α-cells and inappropriately increased serum levels of GCG ( Goke 2008 ). Glucagon-like peptide 1 (GLP1) and other incretin hormones promote glucose

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Li Zhao, Chunfang Zhu, Meng Lu, Chi Chen, Xiaomin Nie, Buatikamu Abudukerimu, Kun Zhang, Zhiyuan Ning, Yi Chen, Jing Cheng, Fangzhen Xia, Ningjian Wang, Michael D Jensen, and Yingli Lu

. 2010 ). Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by gastrointestinal L cells in response to oral nutrient ingestion ( Wan et al . 2017 ) and is an ideal therapy for obesity and T2DM ( Rajeev & Wilding 2016 ). However, native

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Sandra Steensels, Matthias Lannoo, Bert Avau, Jorien Laermans, Laurien Vancleef, Ricard Farré, Kristin Verbeke, and Inge Depoortere

considered as one of the possible mechanisms for the postsurgical metabolic improvements ( Svane et al. 2015 ). RYGB surgery enhances the secretion of the anorexigenic hormones glucagon-like peptide 1 (GLP1) and peptide YY (PYY), and although more

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Adrian Holliday and Andrew Blannin

–tyrosine (PYY) and glucagon-like peptide 1 (GLP-1) have been observed with continuous, high-intensity aerobic bouts of exercise lasting as little as 30 min ( Ueda et al . 2009 a ), and with intermittent exercise bouts yielding energy expenditure values of as

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Shou-Si Lu, Yun-Li Yu, Hao-Jie Zhu, Xiao-Dong Liu, Li Liu, Yao-Wu Liu, Ping Wang, Lin Xie, and Guang-Ji Wang

play is an important role in the regulation of endocrine pancreatic secretion. The intestinal products of the proglucagon gene, glucagon-like peptide-1 (GLP-1), has been shown to contribute significantly to the overall insulin response to oral glucose

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Srilaxmi Kalavalapalli, Fernando Bril, Joy Guingab, Ariana Vergara, Timothy J Garrett, Nishanth E Sunny, and Kenneth Cusi

under investigation for NASH, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown a significant promise for the treatment of NAFLD ( Ding et al. 2006 , Blonde & Russell-Jones 2009 , Cusi 2012 , Armstrong et al. 2013 , 2016 a , b

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Ashley I Taylor, Nigel Irwin, Aine M McKillop, Steven Patterson, Peter R Flatt, and Victor A Gault

has examined the plasma stability and satiety effects of xenin, and further characterised the glucose-lowering and insulinotropic effects of xenin both alongside GIP, glucagon-like peptide-1 (GLP1) and neurotensin. Materials and Methods Degradation of