Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; and.
Am J Physiol Endocrinol Metab. 2014 Jan 15;306(2):E225-31. doi: 10.1152/ajpendo.00563.2013. Epub 2013 Dec 3.
Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial, glucose, insulin, PYY3-36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h) of PYY3-36 were lower (meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05), whereas insulin (meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and ghrelin (meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0-0.5, 4-4.5, and 8-8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P < 0.05). Also, meal-induced fullness was prevented (meal 1, P = 0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia. Furthermore, trends in ghrelin, PYY3-36, and fullness were described by different polynomial functions between the trials. In conclusion, hyperglycemia abolishes meal-induced satiety and dysregulates postprandial responses of the gut hormones PYY3-36 and ghrelin in overweight/obese healthy humans.
高血糖个体的饱腹感和饱腹感调节肠道激素水平异常。我们旨在确定这些异常是否是高血糖的继发结果。10 名健康超重/肥胖受试者（年龄：56 ± 3 岁；BMI：30.3 ± 1.2 kg/m(2)）在无（对照试验）和存在实验性高血糖（高血糖试验；基础值以上 5.4 mM）的情况下，分别在 t = 0、4 和 8 h 时接受了 3 次等热量餐。在整个试验过程中，测量了循环葡萄糖、胰岛素、ghrelin 和肽 YY（PYY）3-36 的水平以及饱腹感的视觉模拟评分。在对照试验中，餐后葡萄糖、胰岛素、PYY3-36 和饱腹感增加，而 ghrelin 减少。在高血糖试验中，血浆葡萄糖升高至 11.2 ± 0.1 mmol/l，PYY3-36 的餐后餐反应（AUC：0-2、4-6 和 8-10 h）降低（餐 1，P < 0.0001；餐 2，P < 0.001；餐 3，P < 0.05），而胰岛素（餐 1，P < 0.01；餐 2，P < 0.001；餐 3，P < 0.05）和 ghrelin（餐 1，P < 0.05；餐 2，P > 0.05；餐 3，P > 0.05）高于对照试验。此外，与对照试验相比，高血糖试验中第一和第三餐的 ghrelin 增量（0-0.5、4-4.5 和 8-8.5 h）反应更高（Δ：2.3 ± 8.0，P = 0.05；Δ：14.4 ± 2.5，P < 0.05）。此外，实验性高血糖还阻止了膳食引起的饱腹感（餐 1，P = 0.06；餐 2，P = 0.01；餐 3，P = 0.08）。此外，在试验之间，ghrelin、PYY3-36 和饱腹感的趋势由不同的多项式函数描述。总之，高血糖可消除超重/肥胖健康人群的膳食诱导饱腹感，并扰乱餐后肠道激素 PYY3-36 和 ghrelin 的反应。
