Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215, Lodz, Poland.
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
Pharmacol Rep. 2021 Dec;73(6):1670-1679. doi: 10.1007/s43440-021-00327-y. Epub 2021 Sep 17.
The role of the incretin hormone, glucagon-like peptide (GLP-1), in Crohn's disease (CD), is still poorly understood. The aim of this study was to investigate whether colitis is associated with changes in blood glucose levels and the possible involvement of the incretin system as an underlaying factor.
We used a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Macroscopic and microscopic score and expression of inflammatory cytokines were measured. The effect of colitis on glucose level was studied by measurement of fasting glucose and GLP-1, dipeptidyl peptidase IV (DPP IV) levels, prohormone convertase 1/3 (PC 1/3) and GLP-1 receptor (GLP-1R) expression in mice. We also measured the level of GLP-1, DPP IV and expression of glucagon (GCG) and PC 1/3 mRNA in serum and colon samples from healthy controls and CD patients.
Fasting glucose levels were increased in animals with colitis compared to controls. GLP-1 was decreased in both serum and colon of mice with colitis in comparison to the control group. DPP IV levels were significantly increased in serum, but not in the colon of mice with colitis as compared to healthy animals. Furthermore, PC 1/3 and GLP-1R expression levels were increased in mice with colitis as compared to controls. In humans, no differences were observed in fasting glucose level between healthy subjects and CD patients. GLP-1 levels were significantly decreased in the serum. Interestingly, GLP-1 level was significantly increased in colon samples of CD patients compared to healthy subjects. No significant differences in DPP IV levels in serum and colon samples were observed between groups.
Changes in the incretin system during colitis seem to contribute to the impaired glucose levels. Differences in incretin levels seem to be modulated by degrading enzyme DPP-IV and PC 1/3. Obtained results suggest that the incretin system may become a novel therapeutic approach in the treatment of CD.
肠促胰岛素激素胰高血糖素样肽（GLP-1）在克罗恩病（CD）中的作用仍知之甚少。本研究旨在探讨结肠炎是否与血糖水平变化相关，以及肠促胰岛素系统是否可能作为潜在的影响因素。
我们使用 2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎小鼠模型。评估宏观和微观评分以及炎症细胞因子的表达。通过测量空腹血糖和 GLP-1、二肽基肽酶 IV（DPP IV）水平、前激素转化酶 1/3（PC 1/3）和 GLP-1 受体（GLP-1R）在小鼠中的表达，研究结肠炎对血糖水平的影响。我们还测量了健康对照组和 CD 患者血清和结肠样本中 GLP-1、DPP IV 和胰高血糖素（GCG）和 PC 1/3 mRNA 的水平。
与对照组相比，结肠炎动物的空腹血糖水平升高。与对照组相比，结肠炎小鼠的血清和结肠中 GLP-1 均降低。与健康动物相比，结肠炎小鼠血清中 DPP IV 水平显著升高，但结肠中无此变化。此外，与对照组相比，结肠炎小鼠的 PC 1/3 和 GLP-1R 表达水平升高。在人类中，健康受试者和 CD 患者之间的空腹血糖水平无差异。GLP-1 水平在血清中显著降低。有趣的是，与健康受试者相比，CD 患者的结肠样本中 GLP-1 水平显著升高。血清和结肠样本中 DPP IV 水平无显著差异。
结肠炎期间肠促胰岛素系统的变化似乎导致血糖水平受损。肠促胰岛素水平的差异似乎受到降解酶 DPP-IV 和 PC 1/3 的调节。研究结果表明，肠促胰岛素系统可能成为治疗 CD 的新的治疗方法。
