目的探讨老年初诊2型糖尿病(T2DM)病人血清淀粉样蛋白A(SAA)、摄食抑制因子-1(Nesfatin-1)、25-羟维生素-D3[25(OH)D3)]水平变化及其与糖脂代谢、胰岛素抵抗的关系。方法选取2017年8月至2019年10月石家庄市第三医院老年初诊T2DM病人106...目的探讨老年初诊2型糖尿病(T2DM)病人血清淀粉样蛋白A(SAA)、摄食抑制因子-1(Nesfatin-1)、25-羟维生素-D3[25(OH)D3)]水平变化及其与糖脂代谢、胰岛素抵抗的关系。方法选取2017年8月至2019年10月石家庄市第三医院老年初诊T2DM病人106例为T2DM组,按1∶1比例选取同期106例健康体检者为健康对照组。对比两组血清SAA、Nesfatin-1、25(OH)D3水平、血糖指标[餐后2 h血糖(2 h PG)、空腹血糖(FBG)]、血脂指标[总胆固醇(TC)、三酰甘油(TG)]、胰岛素敏感性指数(ISI)、胰岛素抵抗指数(HOMA-IR)、餐后2 h胰岛素水平(2 h INS)水平,Pearson相关系数分析老年初诊T2DM病人血清SAA、Nesfatin-1、25(OH)D3水平与糖脂代谢、胰岛素抵抗的相关性。结果 T2DM组血清SAA(564.86±102.53)μg/L、Nesfatin-1(3.06±1.12)μg/L、2 h PG(17.49±3.67)mmol/L、FBG(9.64±2.52)mmol/L、2 h INS(40.29±4.57)mU/L、TC(5.83±1.49)mmol/L、TG(2.92±0.56)mmol/L水平高于健康对照组(496.28±94.42)μg/L、(1.04±0.47)μg/L、(9.58±2.46)mmol/L、(5.31±1.27)mmol/L、(35.63±3.47)mU/L、(4.68±1.26)mmol/L、(1.49±0.47)mmol/L,血清25(OH)D3水平(35.72±5.41)nmol/L低于健康对照组(50.69±6.42)nmol/L(P<0.05);T2DM组ISI(0.46±0.17)低于健康对照组(0.59±0.20),HOMA-IR(5.59±1.04)高于健康对照组(1.69±0.49)(P<0.05);T2DM病人血清SAA、Nesfatin-1水平与2 h PG、FBG、TC、TG、HOMA-IR水平呈正相关,与血清ISI水平呈负相关,血清25(OH)D3水平与2 h PG、FBG、TC、TG、HOMA-IR水平呈负相关,与ISI水平呈正相关(P<0.05)。结论血清SAA、Nesfatin-1在老年初诊T2DM病人中呈高表达,血清25(OH)D3呈低表达,且表达与病人糖脂代谢、胰岛素抵抗关系密切,可作为病情程度评估因子。展开更多
AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS: Caco-2 cells were incub...AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS: Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25(OH)2D3 or with 1 umol/L 1α-25(OH)2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25(OH)2D3 or 1α-25(OH)2D3. 1α-25(OH)2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25(OH)2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS: Both butyrate and 1α-25(OH)2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25(OH)2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25(OH)2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION: Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25(OH)2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25(OH)2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.展开更多
文摘目的探讨老年初诊2型糖尿病(T2DM)病人血清淀粉样蛋白A(SAA)、摄食抑制因子-1(Nesfatin-1)、25-羟维生素-D3[25(OH)D3)]水平变化及其与糖脂代谢、胰岛素抵抗的关系。方法选取2017年8月至2019年10月石家庄市第三医院老年初诊T2DM病人106例为T2DM组,按1∶1比例选取同期106例健康体检者为健康对照组。对比两组血清SAA、Nesfatin-1、25(OH)D3水平、血糖指标[餐后2 h血糖(2 h PG)、空腹血糖(FBG)]、血脂指标[总胆固醇(TC)、三酰甘油(TG)]、胰岛素敏感性指数(ISI)、胰岛素抵抗指数(HOMA-IR)、餐后2 h胰岛素水平(2 h INS)水平,Pearson相关系数分析老年初诊T2DM病人血清SAA、Nesfatin-1、25(OH)D3水平与糖脂代谢、胰岛素抵抗的相关性。结果 T2DM组血清SAA(564.86±102.53)μg/L、Nesfatin-1(3.06±1.12)μg/L、2 h PG(17.49±3.67)mmol/L、FBG(9.64±2.52)mmol/L、2 h INS(40.29±4.57)mU/L、TC(5.83±1.49)mmol/L、TG(2.92±0.56)mmol/L水平高于健康对照组(496.28±94.42)μg/L、(1.04±0.47)μg/L、(9.58±2.46)mmol/L、(5.31±1.27)mmol/L、(35.63±3.47)mU/L、(4.68±1.26)mmol/L、(1.49±0.47)mmol/L,血清25(OH)D3水平(35.72±5.41)nmol/L低于健康对照组(50.69±6.42)nmol/L(P<0.05);T2DM组ISI(0.46±0.17)低于健康对照组(0.59±0.20),HOMA-IR(5.59±1.04)高于健康对照组(1.69±0.49)(P<0.05);T2DM病人血清SAA、Nesfatin-1水平与2 h PG、FBG、TC、TG、HOMA-IR水平呈正相关,与血清ISI水平呈负相关,血清25(OH)D3水平与2 h PG、FBG、TC、TG、HOMA-IR水平呈负相关,与ISI水平呈正相关(P<0.05)。结论血清SAA、Nesfatin-1在老年初诊T2DM病人中呈高表达,血清25(OH)D3呈低表达,且表达与病人糖脂代谢、胰岛素抵抗关系密切,可作为病情程度评估因子。
基金Supported by the Else Kroner-Fresenius Foundation, Bad Homburg, Germany
文摘AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1cx-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells. METHODS: Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 umol/L 25(OH)2D3 or with 1 umol/L 1α-25(OH)2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25(OH)2D3 or 1α-25(OH)2D3. 1α-25(OH)2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25(OH)2D3 protein. Finally, enzymatic activity was measured by ELISA. RESULTS: Both butyrate and 1α-25(OH)2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25(OH)2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25(OH)2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites. CONCLUSION: Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25(OH)2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25(OH)2D3 in combination with butyrate may offer a new therapeutic approach forthe treatment of colon cancer.