title: Increased GLP-1 response after gavage-administration of glucose in UCP2-deficient mice.
abstract: Although it has been widely reported that endogenous level of GLP-1 can be enhanced by various secretagogues, the mechanism of GLP-1 secretion in vivo is still not fully understood. In the present study, we assessed the possible effect of uncoupling protein 2 (UCP2) on GLP-1 secretion in gut. The levels of plasma GLP-1(7-36) amide/(7-37) in UCP2-deficient mice and wild-type mice were measured by applying ELISA technique. UCP2 mRNA and protein levels were detected in the gastrointestinal tract by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The plasma GLP-1 levels in C57BL/6J mice had significantly increased to 6.9 pM (n=8, p<0.001) at 15 min after gavage-administration of glucose (2 g glucose/kg body weight), approximately 2-fold, compared with control group. Plasma GLP-1 levels were also significantly elevated at 30 min (p<0.001), but nearly returned to baseline levels at 60 min. UCP2-deficient mice had higher level of GLP-1 at various time points after administration of glucose (UCP2-deficient mice vs. wild type littermates, 15 min, 9.3±0.9 vs. 6.9±0.3, p<0.001; 30 min, 7.9±0.3 vs. 5.6±0.4, p<0.001; 60 min, 4.9±0.1 vs. 3.3±0.1, p<0.01). UCP2-deficient mice increased GLP-1 response to gavage-administration of glucose. Plasma GLP-1 level was not significantly altered after gavage-administration of saline. This study showed that plasma GLP-1 level increased after gastric glucose challenge, and UCP2 maybe serve as a negative regulator in glucose-induced GLP-1 secretion in mouse gut tract.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University Nanjing, Jiangsu, China. hjzhang06@163.com
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D005951:Glucose Tolerance Test; D007473:Ion Channels / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071246:Uncoupling Protein 2
chemical_list: D001786:Blood Glucose; D007473:Ion Channels; D024101:Mitochondrial Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C055453:glucagon-like peptide 1 (7-36)amide; D052216:Glucagon-Like Peptide 1; D005947:Glucose