Pioglitazone improves insulin secretory capacity and prevents the loss of β-cell mass in obese diabetic db/db mice:: Possible protection of β cells from oxidative stress
Pioglitazone improves insulin secretory capacity and prevents the loss of β-cell mass in obese diabetic db/db mice:: Possible protection of β cells from oxidative stress
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DOI：
10.1016/j.metabol.2003.11.021
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发表时间：
2004-04-01
影响因子：
9.8
通讯作者：
Nagamatsu, S
中科院分区：
文献类型：
--
作者：
Ishida, H;Takizawa, M;Nagamatsu, S
为了评估过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂吡格列酮对糖尿病条件下胰腺13细胞质量减少和功能改变的有益作用，用吡格列酮治疗糖尿病C57BL/KsJ db/db小鼠6周，并评估离体胰岛的胰岛素分泌能力和胰岛素含量。此外，还检查了内分泌胰腺中氧化应激标记物、4-羟基-2-壬烯醛 (HNE) 修饰蛋白和血红素加氧酶-1 的表达，以测量胰腺 β 细胞氧化应激的减少情况。吡格列酮治疗提高了离体胰岛葡萄糖诱导的胰岛素分泌能力及其胰岛素含量（P < .01）。当 13 个细胞用抗胰岛素抗体染色时，用吡格列酮治疗的 db/db 小鼠的细胞表现出强染色，在它们的瘦同窝小鼠中也观察到了这一点。在吡格列酮治疗的 db/db 小鼠胰岛中，氧化应激标记物的免疫染色密度显着降低 (P < .05)。这项研究清楚地证明了吡格列酮长期治疗在降低糖尿病 db/db 小鼠的高血糖和改善葡萄糖诱导的胰岛素分泌能力方面的益处。免疫细胞化学检查的结果表明，这种治疗可减少氧化应激，从而保留 β 细胞质量。因此，吡格列酮治疗可以防止β细胞损伤，并且有助于恢复肥胖糖尿病个体的胰岛素分泌能力。 (C) 2004 Elsevier Inc. 保留所有权利。
In order to assess the beneficial effect of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist pioglitazone on reduction of mass and alteration of function of pancreatic 13 cells under diabetic conditions, diabetic C57BL/KsJ db/db mice were treated with pioglitazone for 6 weeks, and insulin secretory capacity and insulin content of isolated pancreatic islets were evaluated. In addition, the expression of oxidative stress markers, 4-hydroxy-2-nonenal (HNE)-modified proteins and heme oxygenase-1, in endocrine pancreas was examined to measure reduction of oxidative stress in pancreatic beta cells. The capacity for glucose-induced insulin secretion from isolated islets and their insulin content were improved by pioglitazone treatment (P < .01). When 13 cells were stained with anti-insulin antibodies, those of db/db mice treated with pioglitazone exhibited strong staining, as also observed in their lean littermates. The density of immunostaining for oxidative stress markers was significantly reduced in pancreatic islets of pioglitazone-treated db/db mice (P < .05). This study clearly demonstrates the benefit of long-term treatment with pioglitazone in decreasing hyperglycemia and improving glucose-induced insulin secretory capacity in diabetic db/db mice. The results of immunocytochemical examination suggest that this treatment reduces oxidative stress and thereby preserves beta-cell mass. Treatment with pioglitazone thus protects against beta-cell damage and would be useful for restoration of insulin secretory capacity in obese diabetes individuals. (C) 2004 Elsevier Inc. All rights reserved.