Dietary Genistein Influences Number of Acetylcholine Receptors in Female Diabetic Jejunum

BACKGROUND: Intestinal dysfunction in the ob/ob mouse model of diabetes mimics that seen clinically. METHODS: 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 ob/ob and lean mice. RESULTS: Contractility of the jejunum in response to incrementally increasing concentrations of KCl was comparable in ob/ob 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 ob/ob 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 ob/ob mice versus leans, and the genistein diet was without effect. CONCLUSIONS: These data suggest that slowed intestinal transit in the diabetic ob/ob 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 ob/ob mice a genistein-rich diet has potential therapeutic benefits towards improving the debilitating diabetes-related gastrointestinal dysfunction.