Department of Physiology, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA.
Department of Anatomy, Arizona College of Osteopathic Medicine, Midwestern University, 19555 N. 59th Avenue, Glendale, AZ 85308, USA.
J Diabetes Res. 2017;2017:3568146. doi: 10.1155/2017/3568146. Epub 2017 Aug 1.
Intestinal dysfunction in the mouse model of diabetes mimics that seen clinically.
We determined the effects of a 4-week genistein diet (600 mg genistein/kg food) on intestinal function (contractility, morphology, AChR, and motility) in female and lean mice.
Contractility of the jejunum in response to incrementally increasing concentrations of KCl was comparable in females and lean controls regardless of a genistein-diet. There were no changes in the wall thickness measured. We assessed the number of clusters of AChR in the jejunum wall; AChR were decreased by 48% in mice versus leans, and the genistein diet reversed this. In utilizing a video-imaging system to evaluate gastrointestinal motility, we determined that the distance between consecutive contractile events was significantly increased by 1.87-fold in mice versus leans, and the genistein diet was without effect.
These data suggest that slowed intestinal transit in the diabetic mouse may be due in part to decreased AChR and decreased contraction events occurring per unit time. A genistein diet rescues the number of AChR to levels of leans yet did not change the number of contractile events. Feeding mice a genistein-rich diet has potential therapeutic benefits towards improving the debilitating diabetes-related gastrointestinal dysfunction.
糖尿病小鼠模型中的肠道功能障碍与临床上所见相似。
我们确定了为期 4 周的金雀异黄素饮食(600mg 金雀异黄素/公斤食物)对雌性和瘦型小鼠肠道功能(收缩性、形态、AChR 和运动)的影响。
无论是否给予金雀异黄素饮食,对递增浓度 KCl 的回肠收缩反应在糖尿病雌性小鼠和瘦型对照之间是可比的。壁厚度测量没有变化。我们评估了回肠壁中 AChR 簇的数量;与瘦型对照相比,糖尿病小鼠的 AChR 减少了 48%,而金雀异黄素饮食则逆转了这一现象。利用视频成像系统评估胃肠道运动,我们发现糖尿病小鼠连续收缩事件之间的距离显著增加了 1.87 倍,而金雀异黄素饮食没有影响。
这些数据表明,糖尿病小鼠的肠道转运缓慢可能部分归因于 AChR 减少和单位时间内收缩事件减少。金雀异黄素饮食可使 AChR 的数量恢复到瘦型对照的水平,但并未改变收缩事件的数量。给糖尿病小鼠喂食富含金雀异黄素的饮食可能具有改善与糖尿病相关的胃肠道功能障碍的治疗益处。