Dose-related effects of GLP-1 on insulin secretion, insulin sensitivity, and glucose effectiveness in mice

被引:60
作者
Ahrén, B
Pacini, G
机构
[1] Lund Univ, Dept Med, S-20502 Malmo, Sweden
[2] CNR, LADSEB, Inst Syst Sci & Biomed Engn, I-35217 Padua, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1999年 / 277卷 / 06期
关键词
glucagon-like peptide 1; glucose disposal; mouse;
D O I
10.1152/ajpendo.1999.277.6.E996
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We examined the dose-related net effects of glucagon-like peptide 1 (GLP-1) on insulin secretion, insulin sensitivity, and glucose disposal as derived from the minimal model of glucose disappearance in anesthetized mice. GLP-1 dose dependently potentiated insulin secretion after glucose administration, with the half-maximal effect at 1 nmol/kg. GLP-1 also dose dependently reduced the area under the glucose curve (AUC(glucose)) and increased the glucose elimination rate (KG) but did not affect the glucose effectiveness (SG) Furthermore, the insulin sensitivity index (Sr) was reduced after administration of GLP-1. Because insulin secretion was stimulated to a larger degree than SI was reduced, the peptide increased the global disposition index (GDI = AUC(insulin) x S-I). Matching plasma insulin levels after GLP-1 by exogenous insulin reproduced the influences of GLP-1 on AUC(glucose), K-G, S-I, and GDI. Finally, the GLP-1 receptor antagonist exendin-3-(9-39) inhibited the actions of GLP-1. We conclude that GLP-1 increases glucose tolerance in the mouse mainly by potently stimulating insulin secretion.
引用
收藏
页码:E996 / E1004
页数:9
相关论文
共 60 条
[21]   Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1 [J].
Gromada, J ;
Holst, JJ ;
Rorsman, P .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1998, 435 (05) :583-594
[22]   ANTIDIABETOGENIC EFFECT OF GLUCAGON-LIKE PEPTIDE-1 (7-36)AMIDE IN NORMAL SUBJECTS AND PATIENTS WITH DIABETES-MELLITUS [J].
GUTNIAK, M ;
ORSKOV, C ;
HOLST, JJ ;
AHREN, B ;
EFENDIC, S .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (20) :1316-1322
[23]   GLP-1 tablet in type 2 diabetes in fasting and postprandial conditions [J].
Gutniak, MK ;
Larsson, H ;
Sanders, SW ;
Juneskans, O ;
Holst, JJ ;
Ahren, B .
DIABETES CARE, 1997, 20 (12) :1874-1879
[24]   Potential therapeutic level of glucagon-like peptide I achieved in humans by a buccal tablet [J].
Gutniak, MK ;
Larsson, H ;
Heiber, SJ ;
Juneskans, OT ;
Holst, JJ ;
Ahren, B .
DIABETES CARE, 1996, 19 (08) :843-848
[25]   THE INCRETIN NOTION AND ITS RELEVANCE TO DIABETES [J].
HABENER, JF .
ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA, 1993, 22 (04) :775-794
[26]   Effects of glucagon-like peptide-1 (7-36)amide on insulin stimulated rat skeletal muscle glucose transport [J].
Hansen, BF ;
Jensen, P ;
Nepper-Christensen, E ;
Skjolstrup, B .
ACTA DIABETOLOGICA, 1998, 35 (02) :101-103
[27]   GLUCOSE-DEPENDENT ACTION OF GLUCAGON-LIKE PEPTIDE-1(7-37) IN-VIVO DURING SHORT-TERM OR LONG-TERM ADMINISTRATION [J].
HARGROVE, DM ;
NARDONE, NA ;
PERSSON, LM ;
PARKER, JC ;
STEVENSON, RW .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1995, 44 (09) :1231-1237
[28]   TRUNCATED GLUCAGONLIKE PEPTIDE-I, AN INSULIN-RELEASING HORMONE FROM THE DISTAL GUT [J].
HOLST, JJ ;
ORSKOV, C ;
NIELSEN, OV ;
SCHWARTZ, TW .
FEBS LETTERS, 1987, 211 (02) :169-174
[29]  
HOLST JJ, 1997, CURR OPIN ENDOCRINOL, V4, P256
[30]  
HOLTZ GG, 1993, NATURE, V361, P362