Associated Laboratory for Green Chemistry (LAQV) Network of Chemistry and Technology (REQUIMTE), University of Porto, 4050-313 Porto, Portugal.
Department of Immuno-Physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-313 Porto, Portugal.
Int J Mol Sci. 2024 Nov 12;25(22):12115. doi: 10.3390/ijms252212115.
Gastrointestinal complications of diabetes are often overlooked, despite affecting up to 75% of patients. This study innovatively explores local glutathione levels and morphometric changes in the gut of Goto-Kakizaki (GK) rats, a type 2 diabetes animal model. Segments of the intestine, cecum, and colon were collected for histopathological analysis and glutathione quantification. A significant increase in the total thickness of the intestinal wall of GK rats was observed, particularly in the duodenum (1089.02 ± 39.19 vs. 864.19 ± 37.17 µm), ileum (726.29 ± 24.75 vs. 498.76 ± 16.86 µm), cecum (642.24 ± 34.15 vs. 500.97 ± 28.81 µm), and distal colon (1211.81 ± 51.32 vs. 831.71 ± 53.2 µm). Additionally, diabetic rats exhibited thickening of the muscular layers in all segments, except for the duodenum, which was also the only portion where the number of smooth muscle cells did not decrease. Moreover, myenteric neuronal density was lower in GK rats, suggesting neurological loss. Total glutathione levels were lower in all intestinal segments of diabetic rats (except duodenum), and the reduced/oxidized glutathione ratio (GSH/GSSG) was significantly decreased in GK rats, indicating increased oxidative stress. These findings strongly indicate that GK rats undergo significant intestinal remodeling, notable shifts in neuronal populations, and heightened oxidative stress-factors that likely contribute to the functional gastrointestinal alterations seen in diabetic patients.
糖尿病的胃肠道并发症常被忽视，但实际上它们会影响多达 75%的患者。本研究创新性地探讨了 2 型糖尿病动物模型 Goto-Kakizaki（GK）大鼠肠道局部谷胱甘肽水平和形态变化。收集肠道、盲肠和结肠的各个部分进行组织病理学分析和谷胱甘肽定量。GK 大鼠的肠道壁总厚度明显增加，特别是在十二指肠（1089.02 ± 39.19 对 864.19 ± 37.17 µm）、空肠（726.29 ± 24.75 对 498.76 ± 16.86 µm）、盲肠（642.24 ± 34.15 对 500.97 ± 28.81 µm）和远端结肠（1211.81 ± 51.32 对 831.71 ± 53.2 µm）。此外，糖尿病大鼠在所有肠道节段的肌肉层都有增厚，除了十二指肠，这也是唯一平滑肌细胞数量没有减少的部位。此外，GK 大鼠的肌间神经元密度较低，表明存在神经损失。糖尿病大鼠的所有肠道节段的总谷胱甘肽水平均较低（十二指肠除外），并且 GK 大鼠的还原型/氧化型谷胱甘肽比值（GSH/GSSG）显著降低，表明氧化应激增加。这些发现强烈表明，GK 大鼠经历了显著的肠道重塑、神经元群体的显著变化以及氧化应激的增加，这些因素可能导致糖尿病患者出现功能性胃肠道改变。
