Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient fischer rats
Improved glucose tolerance via enhanced glucose-dependent insulin secretion in dipeptidyl peptidase IV-deficient fischer rats
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DOI：
10.1006/bbrc.2001.4999
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发表时间：
2001-06-08
影响因子：
3.1
通讯作者：
Tanaka, I
中科院分区：
文献类型：
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作者：
Nagakura, T;Yasuda, N;Tanaka, I
胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素，可诱导葡萄糖依赖性胰岛素分泌。GLP-1在释放后被二肽基肽酶IV（DPPIV）快速降解。我们研究了DPPIV缺陷的F344/DuCrj大鼠与DPPIV阳性的F344/Jcl大鼠相比是否显示出改善的葡萄糖耐量。口服葡萄糖耐量试验表明F344/DuCrj大鼠的葡萄糖耐量有所改善，但两个品系的血糖水平在葡萄糖推注后120 min几乎相同。DPPIV抑制剂Valine-pyrrolidide对F344/DuCrj大鼠的糖耐量无明显影响，但能改善F344/Jcl大鼠的糖耐量。在十二指肠内葡萄糖耐量试验中检测到胰岛素分泌增强和高血浆活性GLP-1水平。DPPIV缺陷型F344/DuCrj大鼠的葡萄糖耐量通过高活性GLP-1水平介导的胰岛素释放增强而改善。我们的研究结果表明，DPPIV抑制是一种合理的策略，以治疗糖尿病患者，改善葡萄糖耐量低血糖的风险，（C）2001年学术出版社。
Glucagon-like peptide-1 (GLP-1) is an incretin, which induces glucose-dependent insulin secretion. GLP-1 is rapidly degraded by dipeptidyl peptidase IV (DPPIV) after its release. We investigated whether DPPIV-deficient F344/DuCrj rats show improved glucose tolerance when compared with DPPIV-positive F344/Jcl rats. Oral glucose tolerance test indicated improved glucose tolerance in F344/DuCrj rats, but blood glucose levels of the two strains were almost the same 120 min after the glucose bolus. Valine-pyrrolidide, a DPPIV inhibitor, had no effect on the glucose tolerance of F344/DuCrj rats, but improved that of F344/Jcl rats. Enhanced insulin secretion and high plasma active GLP-1 levels were detected in an intraduodenal glucose tolerance test. Glucose tolerance is improved in DPPIV-deficient F344/DuCrj rats via enhanced insulin release mediated by high active GLP-1 levels. Our results suggest that DPPIV inhibition is a rational strategy to treat diabetic patients by improving glucose tolerance with low risk of hypoglycemia, (C) 2001 Academic Press.