他汀类调脂药对大鼠胰岛胰岛素分泌的影响及机制研究

目的 观察不同他汀类药物对大鼠胰岛葡萄糖刺激的胰岛素分泌(GSIS)的抑制作用及机制.方法 新鲜分离或经24 h培养的胰岛均匀分为对照组、阿托伐他汀组、氟伐他汀组和普伐他汀组,对照组给予Kreb-Ringer碳酸氢盐缓冲液,他汀类药物组分别给予100μmol/L阿托伐他汀、氟伐他汀和普伐他汀,水浴30 min或过夜培养24 h.各组经2.8、5.5、11.1、16.7、25.0 mmol/L葡萄糖刺激后,37℃水浴法测定胰岛GSIS变化,生物化学发光法测定三磷酸腺苷(ATP)含量.结果 100μmol/L阿托伐他汀水浴30 min后,在16.7 mmol/L葡萄糖刺激下,与相应对照组比较,ATP含量[(9.54±1.64)pmol/胰岛比(12.33±1.89)pmol/胰岛]及胰岛素分泌(1.60±0.21比2.39±0.30)均下降(P＜0.05);100 μmol/L氟伐他汀过夜培养24 h后,在16.7 mmol/L葡萄糖刺激下,与相应对照组比较,ATP含量[(10.24±2.01)pmol/胰岛比(12.31±2.16)pmol/胰岛]及胰岛素分泌(3.12±0.32比4.17±0.37)也均下降(P＜0.05).结论 阿托伐他汀、氟伐他汀通过抑制胰岛ATP的生成而抑制GSIS,抑制程度与其脂溶性强弱有关.

Abstract：

Objective To evaluate the inhibitory effect of statins on glucose-stimulated insulin secretion (GSIS) of pancreatic islet in rat and to explore its mechanisms. Methods According to the average volume, freshly isolated or 24-hour cultured pancreatic islets were randomly divided into control group( incubated with Kreb-Ringer bicarbonate buffer), the atorvastatin group( incubated with 100 μ mol/L atorvastatin), the fluvastatin group (incubated with 100 μ mol/L fluvastatin)and the pravastatin group (incubated with 100 μ mol/L pravastatin). Stimulated by 2. 8,5. 5,11.1,16. 7 mmol/L and 25.0 mmol/L glucose respectively, the effect of 100 μ mol/L statins on ATP content and GSIS was compared in the four groups. GSIS was performed by the 37℃ bath incubation method and ATP content was measured by chemiluminescence method. Results Incubated with 100 μ mol/L atorvastatin for 30 minutes, in the presence of 16. 7 mmol/L glucose, the ATP content [(9. 54 ± 1. 64) pmol/islet vs ( 12. 33 ± 1.89) pmol/islet] and GSIS (1.60 ± 0. 21 vs 2. 39 ± 0. 30) were significantly reduced in comparison with the control group (P＜0. 05). Cultured with 100 μmol/L fluvastatin for 24 hours, the ATP content [( 10. 24 ±2.01 )pmol/islet vs (12. 31 ±2. 16) pmol/islet] and GSIS (3. 12 ± 0. 32 vs 4. 17 ±0. 37 ) were all significantly decreased at the higher glucose concentration of 16. 7 mmol/L ( P ＜ 0. 05). Conclusion Atorvastatin and fluvastatin may inhibit GSIS by decreasing ATP content in pancreatic islet and the inhibitory effect is related to the strength of its lipophilicity.

Research on the effect of statins on insulin secretion from pancreatic islet in rats and its mechanisms

Objective To evaluate the inhibitory effect of statins on glucose-stimulated insulin secretion (GSIS) of pancreatic islet in rat and to explore its mechanisms. Methods According to the average volume, freshly isolated or 24-hour cultured pancreatic islets were randomly divided into control group( incubated with Kreb-Ringer bicarbonate buffer), the atorvastatin group( incubated with 100 μ mol/L atorvastatin), the fluvastatin group (incubated with 100 μ mol/L fluvastatin)and the pravastatin group (incubated with 100 μ mol/L pravastatin). Stimulated by 2. 8,5. 5,11.1,16. 7 mmol/L and 25.0 mmol/L glucose respectively, the effect of 100 μ mol/L statins on ATP content and GSIS was compared in the four groups. GSIS was performed by the 37℃ bath incubation method and ATP content was measured by chemiluminescence method. Results Incubated with 100 μ mol/L atorvastatin for 30 minutes, in the presence of 16. 7 mmol/L glucose, the ATP content [(9. 54 ± 1. 64) pmol/islet vs ( 12. 33 ± 1.89) pmol/islet] and GSIS (1.60 ± 0. 21 vs 2. 39 ± 0. 30) were significantly reduced in comparison with the control group (P＜0. 05). Cultured with 100 μmol/L fluvastatin for 24 hours, the ATP content [( 10. 24 ±2.01 )pmol/islet vs (12. 31 ±2. 16) pmol/islet] and GSIS (3. 12 ± 0. 32 vs 4. 17 ±0. 37 ) were all significantly decreased at the higher glucose concentration of 16. 7 mmol/L ( P ＜ 0. 05). Conclusion Atorvastatin and fluvastatin may inhibit GSIS by decreasing ATP content in pancreatic islet and the inhibitory effect is related to the strength of its lipophilicity.