| Objective: To explore the expressions of PPAR-α, PPAR-γ, inflammatory mediators, apoptotic regulator caspase-3, and apoptotic level in pancreatic islets by establish obese rat models induced by high-fat and high-sucrose diets. To investigate the effects of the peroxisome proliferators-activator receptor(PPAR)-α agonist fenofibrate and PPAR-γ agonist pioglitazone on function and apoptosis of islets.Methods: S-D obese rat models were established with high-sucrose diet (including high-sucrose diet (co group), high sucrose diet with fenofibrate (cf group) or pioglitazone (cp group) treatment) and high-fat diet (including high-fat diet (fo group), high-fat diet with fenofibrate (ff group) or pioglitazone (fp group)treatment), while the control rats were with normal diet (control group). After 8-10 weeks intervention, immunohistochemistry and western blot were performed to evaluate the expressions of insulin, glucagons, ss, PPAR- α , PPAR- γ, NF-κB, I-κB, P38, ERK1 and caspase-3 proteins in islets, in situ hybridization and RT-PCR were underwent to access the mRNA levels of PPAR- α , PPAR- γ , NF-κB and caspase-3. At the same time, apoptotic level were evaluated by TUNEL, and islets mass were scored in tissue slides. Results: 1) Islets mass enlarged in co and fo groups. The compositions of islet cells were as same as the control. The expression of insulin was lower in co and fo groups than the control, but after using pioglitazone, less islets mass and more insulin expression were found in cp and fp groups. 2) Comparing with the control group,expressions levels of PPAR- a , PPAR- Y protein and mRNA were reduced in co and fo group, and the expression of PPAR- a protein and mRNA increased in cf and ff groups, the expression of PPAR- Y protein and mRNA elevated in cp and fp groups. 3) The levels of NF-kB, P38, ERK1 proteins and mRNA increased significantly in fo group, the expressions of NF-kB, P38 decreased in ff and fp groups, the level of ERK1 only decreased in fp group, the protein level of I-kB was no difference among control, co and fo group, and I-kB increased in cf and ff groups. 4) In control group, the expression of caspase-3 was lowest, and elevated gradually in co and fo groups, the level of caspase-3 decreased in cf, cp, ff and fp groups comparing with co and fo groups. Few TUNEL-position cells were found in all the groups.Conclusion: In the obese rat models induced by high-sucrose and high-fat diets, islets mass enlarged, but insulin level decreased; The expressions of PPAR- a and PPAR- Y in islets decreased significantly, and the level of several inflammatory mediators and caspase-3 increased in islets of obese rat model. Though no evidence of inflammatory response and apoptosis were detected, the dysfunction of inflammatory and apoptotic redulators already existed in islets of obese rats. Fenofibrate and pioglitazone could protect P cells function and survival by corrected inflammatory and apoptotic regulation.
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