目的研究小檗碱对胰岛素抵抗模型肝细胞11β-羟基类固醇脱氢酶1（11β-HSD1）mRNA表达的影响。方法应用高浓度胰岛素孵育HepG2细胞24h，建立胰岛素抵抗肝细胞模型。将模型细胞分别置于含不同浓度胰岛素和小檗碱的培养液中培养24h，以葡...目的研究小檗碱对胰岛素抵抗模型肝细胞11β-羟基类固醇脱氢酶1（11β-HSD1）mRNA表达的影响。方法应用高浓度胰岛素孵育HepG2细胞24h，建立胰岛素抵抗肝细胞模型。将模型细胞分别置于含不同浓度胰岛素和小檗碱的培养液中培养24h，以葡萄糖氧化酶-过氧化物酶（GOD-POD）法测定培养液中的葡萄糖浓度，计算细胞对葡萄糖的吸收率。应用RT-PCR检测小檗碱作用前后模型细胞11β-HSD1mRNA的表达。结果以含10-7mol／L胰岛素的培养液孵育HepG2细胞24h后，细胞对葡萄糖的吸收明显降低，表明建模成功。模型细胞经高浓度（10μmol／L）小檗碱处理后，葡萄糖吸收率明显增加[（42．53±1．99）％VS（28．16±1．99）％，t=12．9457，P〈0．01]，并且高浓度小檗碱与胰岛素对模型细胞有协同促进葡萄糖吸收的作用。模型细胞11β—HSD 1mRNA表达显著高于非胰岛素抵抗细胞（相对表达量：4．60±0．96 vs 0．67±0．42，t=4．9476，P〈0．05）。经高浓度小檗碱干预24h后，模型细胞11β-HSD1mRNA表达降低，与非胰岛素抵抗HepG2细胞相比差异无统计学意义（相对表达量：1．12±0．35VS0．67±0．42，t=1．1394，P〉0．05）。低浓度（1μmol／L）小檗碱则作用不明显。结论浓度依赖性地下调11β—HSD1mRNA表达是小檗碱改善胰岛素抵抗的作用机制之一。展开更多
过量激素刺激骨髓间质干细胞(bone marrow stromal cells,BMSCs)使得成骨能力减弱、成脂能力增强是导致股骨头坏死(osteonecrosis of the femoral head,ONFH)的主要原因,调控机制尚未阐明。最新的研究发现激素引起骨组织中11β-HSD1活...过量激素刺激骨髓间质干细胞(bone marrow stromal cells,BMSCs)使得成骨能力减弱、成脂能力增强是导致股骨头坏死(osteonecrosis of the femoral head,ONFH)的主要原因,调控机制尚未阐明。最新的研究发现激素引起骨组织中11β-HSD1活性增强,导致骨局部内源性激素积聚可抑制骨形成。抑制11β-HSD1活性可促进成骨细胞分化,抑制脂肪分化。故推测内源性激素在ONFH的发病过程中起到重要作用,在激素与BMSCs活性变化之间可能存在11β-HSD1调控的内源性激素代谢途径参与ONFH的发病过程。因此,深入研究11β-HSD1介导的内源性激素代谢途径在ONFH发病中的作用,对深入了解ONFH的发病机制具有重要意义。展开更多
Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide vari...Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of < 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucosecotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.展开更多
文摘目的研究小檗碱对胰岛素抵抗模型肝细胞11β-羟基类固醇脱氢酶1（11β-HSD1）mRNA表达的影响。方法应用高浓度胰岛素孵育HepG2细胞24h，建立胰岛素抵抗肝细胞模型。将模型细胞分别置于含不同浓度胰岛素和小檗碱的培养液中培养24h，以葡萄糖氧化酶-过氧化物酶（GOD-POD）法测定培养液中的葡萄糖浓度，计算细胞对葡萄糖的吸收率。应用RT-PCR检测小檗碱作用前后模型细胞11β-HSD1mRNA的表达。结果以含10-7mol／L胰岛素的培养液孵育HepG2细胞24h后，细胞对葡萄糖的吸收明显降低，表明建模成功。模型细胞经高浓度（10μmol／L）小檗碱处理后，葡萄糖吸收率明显增加[（42．53±1．99）％VS（28．16±1．99）％，t=12．9457，P〈0．01]，并且高浓度小檗碱与胰岛素对模型细胞有协同促进葡萄糖吸收的作用。模型细胞11β—HSD 1mRNA表达显著高于非胰岛素抵抗细胞（相对表达量：4．60±0．96 vs 0．67±0．42，t=4．9476，P〈0．05）。经高浓度小檗碱干预24h后，模型细胞11β-HSD1mRNA表达降低，与非胰岛素抵抗HepG2细胞相比差异无统计学意义（相对表达量：1．12±0．35VS0．67±0．42，t=1．1394，P〉0．05）。低浓度（1μmol／L）小檗碱则作用不明显。结论浓度依赖性地下调11β—HSD1mRNA表达是小檗碱改善胰岛素抵抗的作用机制之一。
文摘过量激素刺激骨髓间质干细胞(bone marrow stromal cells,BMSCs)使得成骨能力减弱、成脂能力增强是导致股骨头坏死(osteonecrosis of the femoral head,ONFH)的主要原因,调控机制尚未阐明。最新的研究发现激素引起骨组织中11β-HSD1活性增强,导致骨局部内源性激素积聚可抑制骨形成。抑制11β-HSD1活性可促进成骨细胞分化,抑制脂肪分化。故推测内源性激素在ONFH的发病过程中起到重要作用,在激素与BMSCs活性变化之间可能存在11β-HSD1调控的内源性激素代谢途径参与ONFH的发病过程。因此,深入研究11β-HSD1介导的内源性激素代谢途径在ONFH发病中的作用,对深入了解ONFH的发病机制具有重要意义。
文摘Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of < 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucosecotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.
