The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

被引:78
作者
Meier, JJ
Gethmann, A
Nauck, MA
Götze, O
Schmitz, F
Deacon, CF
Gallwitz, B
Schmidt, WE
Holst, JJ
机构
[1] Ruhr Univ Bochum, St Josef Hosp, Dept Med 1, D-44791 Bochum, Germany
[2] Diabet Zentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
[3] Univ Copenhagen, Panum Inst, Dept Med Biophys, DK-1168 Copenhagen, Denmark
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2006年 / 290卷 / 06期
关键词
insulin secretion; gastric emptying; incretin hormones; glucose homeostasis;
D O I
10.1152/ajpendo.00576.2005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glucagon- like peptide 1 ( GLP- 1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP1-( 7 - 36) amide is degraded to the metabolite GLP- 1-( 9 - 36) amide. The effects of GLP- 1-( 9 - 36) amide in humans are less well characterized. Fourteen healthy volunteers were studied with intravenous infusion of GLP- 1-( 7 - 36) amide, GLP- 1-( 9 - 36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP- 1 ( total and intact), glucose, insulin, C- peptide, and glucagon measurements. Administration of GLP- 1-( 7 - 36) amide and GLP- 1-( 9 - 36) amide significantly raised total GLP- 1 plasma levels. Plasma concentrations of intact GLP- 1 increased to 21 +/- 5 pmol/ l during the infusion of GLP- 1-( 7 36) amide but remained unchanged during GLP- 1-( 9 - 36) amide infusion [ 5 +/- 3 pmol/ l; P < 0.001 vs. GLP- 1-( 7 - 36) amide administration]. GLP- 1-( 7 - 36) amide reduced fasting and postprandial glucose concentrations ( P < 0.001) and delayed gastric emptying ( P < 0.001). The GLP- 1 metabolite had no influence on insulin or C-peptide concentrations. Glucagon levels were lowered by GLP- 1-( 7 36) amide but not by GLP- 1-( 9 - 36) amide. However, the postprandial rise in glycemia was reduced significantly ( by similar to 6 mg/ dl) by GLP- 1( 9 - 36) amide ( P < 0.05). In contrast, gastric emptying was completely unaffected by the GLP- 1 metabolite. The GLP- 1 metabolite lowers postprandial glycemia independently of changes in insulin and glucagon secretion or in the rate of gastric emptying. Most likely, this is because of direct effects on glucose disposal. However, the glucose-lowering potential of GLP- 1-( 9 - 36) amide appears to be small compared with that of intact GLP- 1-( 7 - 36) amide.
引用
收藏
页码:E1118 / E1123
页数:6
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