An incretin hormone
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Glucagon-like peptide-1 (GLP-1) (1-37) is a 37-residue incretin hormone that is cleaved in vivo into active truncated forms.[1] GLP-1 (1-37) decreases plasma glucose level in high-fat-fed mice when administered at 25 nmol/kg but does not affect plasma insulin level.[2] Pretreament with GLP-1 (1-37) (24 nmol/kg) prevents blood glucose increases in fasted and glucose challenged mice with diabetes induced by streptozotocin.[3] It inhibits polyphagia and polydipsia in STZ-induced diabetic mice 10 and 20 days, respectively, following initiation of GLP-1 (1-37) administration at a dose of 24 nmol/kg. Pretreament with GLP-1 (1-37) (24 nmol/kg) also inhibits loss of pancreatic islets and global and pancreatic oxidative stress in mice with STZ-induced diabetes.
Reference:
[1]. Baggio, L.L., and Drucker, D.J. Biology of incretins: GLP-1 and GIP. Gastroenterology 132(6), 2131-2157 (2007).
[2]. Lennox, R., Porter, D.W., Flatt, P.R., et al. (Val8)GLP-1-Glu-PAL: A GLP-1 agonist that improves hippocampal neurogenesis, glucose homeostasis, and β-cell function in high-fat-fed mice. ChemMedChem 8(4), 595-602 (2013).
[3]. Wu, Y.-L., Huang, J., Liu, J., et al. Protective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) pretreatment in STZ-induced diabetic mice. J. Pept. Sci. 17(7), 499-504 (2011).
Cell experiment: | HEK293 cells (5×104) are seeded in a 96-well plate and transiently cotransfected with the GLP-1R plasmid and the CRE-luciferase reporter plasmid. After a 48 h transfection, different concentrations of GLP-1(1–37) or GLP-1(7–37) are added, and the cells are incubated for 5 h. The cells are harvested for a luciferase assay using a luciferase assay[1]. |
Animal experiment: | Mice[1]The normal KM mice are fasted for 16 h before the administration (i.p.) of GLP-1 and glucose. GLP-1(1-37) (25 nmol/kg) with or without exendin(9-39) (250 nmol/kg) is given in combination with glucose (4 g/kg). GLP-1(7-37) (25 nmol/kg) with or without exendin(9-39) (250 nmol/kg) is also administrated in combination with glucose (4 g/kg). The control group is treated with saline (NaCl, 9 g/l) and glucose (4 g/kg). The IPGTT is carried out at 0, 15, 30 and 60 min after glucose and protein administration, and the blood glucose levels are measured as described above[1]. |
参考文献: [1]. Zhao L, et al. Glucagon-like peptide-1(1-37) can enhance blood glucose homeostasis in mice. Regul Pept. 2012 Oct 10;178(1-3):1-5. |
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