Objective To explore whether tea polyphenols (TP) improve islet β-cell dedifferentiation in aged rats with type 2 diabetes(T2DM). Methods Forty 2-month-old male SD rats were adaptively fed for 1 week, then randomly divided into the control group (control,CON, n=10) and the aging T2DM model group (n=30). The aging T2DM model group rats were fed a high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily. After 4 weeks, the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ). After 2 weeks STZ injection, fasting blood glucose (FBG) greater than or equal to 16.7 mmol/L was defined as successful T2DM model. The successful model rats were randomly divided into aging T2DM group (model, MOD), 300 mg/kg TP group (TP) and 3 mg/kg rosiglitazone group (RSG) according to FBG, with 10 rats in each group. Rats were treated with 50 mg/kg D-galactose and fed with the high-sugar and high-fat diet in the following 8 weeks. Western blot was used to detect the expression of P53 protein in pancreatic tissue of the model group at the end of the experiment, which was higher than that of the CON group, indicating that the aging T2DM model was successfully established. FBG was measured by the blood glucose meter, fasting serum insulin by ELISA, HOMA-IR and HOMA-β calculated. The pathological changes of pancreas were observed after HE staining, and the protein expression of Pdx1, MafA, Ngn3, FoxO1 and p-FoxO1 in the pancreas was detected by Western blot. Results Compared with the CON group, the level of FBG and the expression of P53 in the MOD group were increased (P<0.01). The expression of Pdx1, MafA and the ratio of p-FoxO1/FoxO1 were reduced(P<0.01). The expression of Ngn3 was increased (P<0.01). The level of HOMA-IR was increased (P<0.01). The level of HOMA-β was reduced (P<0.01). The pancreatic tissue showed irregular islet shape, enlarged islet area and blurred boundary with surrounding tissue. Some islet cells had loose or vacuolated cytoplasm. Compared with the MOD group, the expression of P53 and the level of FBG in the rats treated with TP were down-regulated (P<0.05, P<0.01). The expression of Pdx1, MafA and the ratio of p-FoxO1/FoxO1 were increased (P<0.01, P<0.05, P<0.05). The expression of Ngn3 was reduced (P<0.01). Meanwhile, the level of FBG in the rats treated with RSG were down-regulated (P<0.05). The expression of Pdx1, MafA and the ratio of p-FoxO1/FoxO1 were increased (P<0.01, P<0.05, P<0.05). The expression of Ngn3 was reduced (P<0.05). The level of HOMA-IR in the rats treated wih TP or RSG was reduced (P<0.05). In addition, the islet shape was improved, the islet area was smaller, and the degree of loose cytoplasm or vacuolization of islet cells was reduced. Conclusion TP can improve the dedifferentiation of islet β cells in the aged T2DM model rats, and its mechanism is related to up-regulatd phosphorylation level of FoxO1.
Key words
tea polyphenols /
aged T2DM /
β-cell dedifferentiation /
FoxO1
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