Improvement of glucose tolerance by rhein with restored early-phase insulin secretion in db/db mice

Aims: In the present study, we investigated whether rhein exerted hypoglycemic action and rhein’s effect on the pancreatic β cell in db/db mice. Materials and methods: Thirty 4-week-old db/db mice were randomized to treatment with rhein (120 mg/kg) (no.=15) and placebo (1% natrium cellulose solution) (no.=15) for 8 weeks, respectively. Fifteen age-matched non-diabetic littermates db/m mice treated with placebo were studied as non-diabetic control. After an 8-week treatment, ip glucose tolerance test (IPGTT) and arginine tolerance test were performed. Area under curve (AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. Immunohistochemical staining of insulin was performed to estimate β cell mass. TUNEL assay was performed to determine β cell apoptosis. Islet isolation and perifusion were performed to evaluate kinetics of insulin release in vitro, especially first-phase insulin. Results: Compared with control group, AUC of glucose concentrations significantly decreased in the rhein-treated group (p<0.05). Simultaneously, AUC of insulin levels increased in the rhein-treated group (p<0.05), especially in the first 30 min after glucose load. Perifusion showed that the rhein-treated group manifested a significantly increase of first-phase insulin secretion. Immunohistochemical study and TUNEL assay showed that rhein treatment greatly preserved β cell mass and inhibited β cell apoptosis. Conclusions: Rhein treatment significantly improved glucose-dependent and independent insulin secretion by preservation of β cell mass and inhibition of β cell apoptosis in db/db mice. The characteristics of rhein may make it a novel therapeutic means for preventing from or curing diabetes in the near future.