Ahrén B, Lindskog S, van Dijk G, Scheurink A J, Steffens A B
Department of Medicine, Lund University, Malmö, Sweden.
Endocr Res. 1995 Aug;21(3):583-94. doi: 10.1080/07435809509030475.
The truncated glucagon-like peptide-1 (GLP-1(7-36)amide or GLP-1) stimulates insulin secretion, enhances glucose elimination and is of potential interest in diabetes treatment. We studied the hypoglycemic action of GLP-1 in normal mice when given alone or together with the fructose analogue, 2,5-anhydro-D-mannitol (2,5-AM), which inhibits glycogenolysis and gluconeogenesis. GLP-1 (32 nmol/kg iv) lowered plasma glucose levels after 25 min to 4.6 +/- 0.2 mmol/l compared with 7.3 +/- 0.4 mmol/l in controls (P < 0.001). Also 2,5-AM (0.5 mumol/kg iv) reduced plasma glucose levels, to 5.6 +/- 0.3 mmol/l (P < 0.01). When given together, the glucose lowering action of GLP-1 and 2,5-AM was additive, since the 25 min glucose level was 2.8 +/- 0.2 mmol/l. At 5 min after injection, GLP-1 had increased plasma insulin levels to 693 +/- 68 pmol/l compared with 342 +/- 42 pmol/l in controls (P < 0.01). 2,5-AM abolished this increase. Furthermore, GLP-1 (32 nmol/kg) did not affect the glycogen content, neither in the liver nor in the gastrocnemic muscle in samples taken at 30 min after injection. Moreover, in isolated islets incubated at 3.3 and 8.3 mmol/l glucose, 2,5-AM at 75 mmol/l inhibited glucose-stimulated insulin secretion (P < 0.05) showing that 2,5-AM inhibits insulin secretion both in vivo and in vitro. We conclude that GLP-1 may reduce plasma glucose levels also to levels below the basal levels under normal conditions, and that an insulin- and liver-independent action of the peptide contributes to its hypoglycemic action in normal animals.
截短的胰高血糖素样肽-1（GLP-1(7 - 36)酰胺或GLP-1）可刺激胰岛素分泌，增强葡萄糖清除，在糖尿病治疗中具有潜在价值。我们研究了单独给予GLP-1或与果糖类似物2,5-脱水-D-甘露糖醇（2,5-AM）联合给予时，GLP-1在正常小鼠中的降血糖作用，2,5-AM可抑制糖原分解和糖异生。静脉注射GLP-1（32 nmol/kg）25分钟后，血浆葡萄糖水平降至4.6±0.2 mmol/L，而对照组为7.3±0.4 mmol/L（P<0.001）。同样，静脉注射2,5-AM（0.5 μmol/kg）可使血浆葡萄糖水平降至5.6±0.3 mmol/L（P<0.01）。联合给予时，GLP-1和2,5-AM的降血糖作用是相加的，因为25分钟时的葡萄糖水平为2.8±0.2 mmol/L。注射后5分钟，GLP-1使血浆胰岛素水平升至693±68 pmol/L，而对照组为342±42 pmol/L（P<0.01）。2,5-AM消除了这种升高。此外，注射后30分钟采集的样本中，GLP-1（32 nmol/kg）对肝脏和腓肠肌中的糖原含量均无影响。此外，在葡萄糖浓度为3.3和8.3 mmol/L的分离胰岛中，75 mmol/L的2,5-AM可抑制葡萄糖刺激的胰岛素分泌（P<0.05），表明2,5-AM在体内和体外均抑制胰岛素分泌。我们得出结论，GLP-1在正常条件下也可将血浆葡萄糖水平降低至基础水平以下，并且该肽的胰岛素和肝脏非依赖性作用有助于其在正常动物中的降血糖作用。
