Genistein Reduces Hyperglycemia and Islet Cell Loss in a High-Dosage Manner in Rats With Alloxan-Induced Pancreatic Damage

Objectives: Elucidate whether genistein (a soy-derived isoflavone) possesses the capacity to alleviate hyperglycemia and minimize islet cell loss after the onset of diabetes and whether the beneficial effect of genistein is dosage dependent. Methods: Alloxan-induced diabetic male Sprague-Dawley rats were randomly divided into 5 groups (10 rats per group) and treated with saline, vehicle, and 3 different dosages of genistein by daily gavage. Blood glucose and insulin levels, body weight, and oral glucose tolerance test were assessed; histological changes in pancreatic islets were quantified. In addition, rat islets were isolated, cultured, and exposed to alloxan in the presence or absence of genistein. The survival and the proliferation of islet cells were assessed, and insulin levels in the culture supernatant were measured. Results: In vivo high-dose (30 mg/kg per day) but not low-dose genistein significantly decreases weight loss, hyperglycemia, and islet cell loss in alloxan-induced diabetic rats, while increasing blood insulin levels and glucose tolerance. In vitro experiments reveal that genistein improves islet cell survival and proliferation and facilitates insulin production after alloxan injury. Conclusions: Genistein possesses the capacity to reduce hyperglycemia via minimization of islet cell loss in a dosage-dependent manner (estimating >5-fold than physical intakes) after the onset of diabetes.