Hayakawa Masaki, Hira Tohru, Nakamura Masako, Iida Tetsuo, Kishimoto Yuka, Hara Hiroshi
Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan; Research Faculty of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
Biochem Biophys Res Commun. 2018 Feb 2. doi: 10.1016/j.bbrc.2018.01.128.
Glucagon-like peptide 1 (GLP-1), an incretin gastrointestinal hormone, is secreted when stimulated by nutrients including metabolizable sugars such as glucose and fructose. d-Allulose (allulose), also known as d-psicose, is a C-3 isomer of d-fructose and a rare sugar with anti-diabetic or anti-obese effects in animal models. In the present study, we examined whether an oral administration of allulose could stimulate GLP-1 secretion in rats, and investigated the underlying mechanisms. Oral, but not intraperitoneal, administration of allulose (0.5-2.0 g/kg body weight) elevated plasma GLP-1 levels for more than 2 h in a dose-dependent manner. The effects of allulose on GLP-1 secretion were higher than that of dextrin, fructose, or glucose. In addition, oral allulose increased total and active GLP-1, but not glucose-dependent insulinotropic polypeptide (GIP), levels in the portal vein. In anesthetized rats equipped with a portal catheter, luminal (duodenum and ileum) administration of allulose increased portal GLP-1 levels, indicating the luminal effect of allulose. Allulose-induced GLP-1 secretion was abolished in the presence of xanthohumol (a glucose/fructose transport inhibitor), but not in the presence of inhibitors of the sodium-dependent glucose cotransporter 1 or the sweet taste receptor. These results demonstrate a potent and lasting effect of orally administered allulose on GLP-1 secretion in rats, without affecting GIP secretion. The potent and selective GLP-1-releasing effect of allulose holds promise for the prevention and treatment of glucose intolerance through promoting endogenous GLP-1 secretion.
胰高血糖素样肽1（GLP-1）是一种肠促胰岛素胃肠激素，在受到包括葡萄糖和果糖等可代谢糖在内的营养物质刺激时分泌。d-阿洛酮糖（阿洛酮糖），也称为d-塔格糖，是d-果糖的C-3异构体，是一种在动物模型中具有抗糖尿病或抗肥胖作用的稀有糖。在本研究中，我们研究了口服阿洛酮糖是否能刺激大鼠GLP-1分泌，并探讨其潜在机制。口服（而非腹腔注射）阿洛酮糖（0.5 - 2.0 g/kg体重）以剂量依赖的方式使血浆GLP-1水平升高超过2小时。阿洛酮糖对GLP-1分泌的作用高于糊精、果糖或葡萄糖。此外，口服阿洛酮糖可增加门静脉中总GLP-1和活性GLP-1水平，但不增加葡萄糖依赖性促胰岛素多肽（GIP）水平。在配备门静脉导管的麻醉大鼠中，向肠腔（十二指肠和回肠）给药阿洛酮糖可增加门静脉GLP-1水平，表明阿洛酮糖具有肠腔效应。在存在黄腐酚（一种葡萄糖/果糖转运抑制剂）的情况下，阿洛酮糖诱导的GLP-1分泌被消除，但在存在钠依赖性葡萄糖共转运蛋白1或甜味受体抑制剂的情况下则不会。这些结果表明，口服阿洛酮糖对大鼠GLP-1分泌具有强大而持久的作用，且不影响GIP分泌。阿洛酮糖强大且选择性的GLP-1释放作用有望通过促进内源性GLP-1分泌来预防和治疗葡萄糖不耐受。
