Orally Administered Glucagon-Like Peptide-1 Affects Glucose Homeostasis Following an Oral Glucose Tolerance Test in Healthy Male Subjects

被引:38
作者
Steinert, R. E. [1 ,3 ]
Poller, B. [2 ]
Castelli, M. C. [4 ]
Friedman, K. [4 ]
Huber, A. R. [5 ]
Drewe, J. [1 ,2 ]
Beglinger, C. [1 ,3 ]
机构
[1] Univ Basel Hosp, Dept Biomed, Clin Res Ctr, CH-4031 Basel, Switzerland
[2] Univ Basel Hosp, Dept Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland
[3] Univ Basel Hosp, Div Gastroenterol, CH-4031 Basel, Switzerland
[4] Emisphere Technol, Tarrytown, NY USA
[5] Kantonsspital Aarau, Ctr Lab Med, Aarau, Switzerland
基金
瑞士国家科学基金会;
关键词
PROOF-OF-CONCEPT; INCRETIN HORMONE; INSULINOTROPIC ACTION; NONDIABETIC SUBJECTS; DIABETIC-PATIENTS; TEST MEAL; SECRETION; GLP-1; AMIDE; PHARMACOKINETICS;
D O I
10.1038/clpt.2009.159
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Glucagon-like peptide-1 (GLP-1) exerts several effects on glucose homeostasis and reduces food intake. After its release from intestinal L cells, GLP-1 is subject to (i) rapid breakdown by dipeptidyl peptidase IV and (ii) high liver extraction. The highest concentrations of GLP-1 are found in the splanchnic blood rather than in the systemic circulation. An oral delivery system would mimic endogenous secretion. Here we investigated the pharmacokinetic/pharmacodynamic (PK/PD) effects of a single dose (2 mg) of oral GLP-1 administered prior to an oral glucose tolerance test (OGTT) in 16 healthy males. GLP-1 was rapidly absorbed from the gut, leading to tenfold higher plasma concentrations compared with controls. The PD profile was consistent with reported pharmacology; GLP-1 significantly stimulated basal insulin release (P < 0.027), with marked effects on glucose levels. The postprandial glucose peak was delayed with GLP-1, suggesting an effect on gastric emptying.
引用
收藏
页码:644 / 650
页数:7
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