Effect of early intervention with rhein on islet function in db/db mice / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the hypoglycemic action of rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), one of the anthraquinone derivatives isolated from rhubarb, and study its effects on pancreatic beta-cells in db/db mice.</p><p><b>METHODS</b>Thirty 4-week-old db/db mice were randomized for an 8-week treatment with intragastric administration of rhein (120 mg/kg, n=15) or placebo (1% natrium cellulose solution, n=15). After the treatment, intraperitoneal glucose tolerance test (IPGTT) was performed and the area under curve (AUC) of insulin levels in IPGTT was calculated to evaluate insulin secretory function. The AUC(INS0-30) was calculated to evaluate the early-phase insulin secretion. Immunohistochemical staining for insulin was performed to estimate the beta-cell mass, and beta-cell apoptosis was detected using TUNEL assay.</p><p><b>RESULTS</b>Compared with the control group, rhein-treated group showed significantly reduced blood glucose concentrations at 0, 30, 60 and 120 min after glucose load with significantly higher insulin levels at 30, 60 and 120 min. The early-phase insulin secretion was also obviously increased. The beta-cell mass was obviously rescued by the 8-week treatment with rhein, which also notably improved the staining intensity of insulin and suppressed beta-cell apoptosis compared with the control.</p><p><b>CONCLUSIONS</b>Early rhein treatment significantly improves glucose tolerance by restoring the early-phase insulin secretion in db/db mice and inhibiting the apoptosis of the beta-cells, suggesting the potential of rhein as a novel therapeutic agent for type 2 diabetes.</p>