Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients
Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients
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DOI：
10.1007/s125-002-8248-z
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发表时间：
2002-01-01
期刊：
影响因子：
8.2
通讯作者：
Yagihashi, S
中科院分区：
文献类型：
--
作者：
Sakuraba, H;Mizukami, H;Yagihashi, S
目的/假设。我们检查了日本II型糖尿病患者的胰岛病变，以确定损伤是否与氧化应激有关。对14例糖尿病患者和15例非糖尿病患者胰腺尾部的免疫染色切片进行形态学分析。通过刚果红染色和免疫染色评价淀粉样蛋白沉积和氧化应激诱导的组织损伤。抗氧化应激能力进行了评估，从铜，锌-超氧化物歧化酶（SOD）的免疫染色结果。原位杂交检测胰岛素原mRNA的表达。糖尿病患者胰腺中约15%的胰岛淀粉样蛋白沉积，8-OHdG和HNE反应增强，SOD表达减少。糖尿病患者胰岛β细胞体积密度和胰腺总β细胞质量分别降低22%（p < 0.001）和30%（p < 0.05）。糖尿病患者的胰岛体积密度和（原）胰岛素mRNA阳性细胞的总质量同样分别减少了22%（p < 0.001）和39%（p < 0.05）。A细胞的胰岛体积密度增加了20%（p < 0.001），但总质量没有变化。胰岛、D和PP细胞的体积密度无变化。β细胞体积密度降低与8-OHdG阳性染色增加相关。日本II型糖尿病患者表现出β细胞质量减少和与β细胞病变程度相关的氧化应激相关组织损伤增加的证据。
Aims/hypothesis. We examined the pancreatic islet lesions in Japanese patients with Type II diabetes mellitus to determine if the damage was related to oxidative stress.Methods. Morphometric analyses were performed on immunostained sections of the tail portion of the pancreas from 14 diabetic and 15 non-diabetic patients. Amyloid deposition and oxidative stress-induced tissue damage were evaluated by Congo-red staining and immunostaining. Resistance to oxidative stress was assessed from immunostaining results for Cu, Zn-superoxide dismutase (SOD). Expression of (pro)insulin mRNA was assessed by in situ hybridisation.Results. The pancreas from diabetic patients had amyloid deposition in about 15 % of the islets, intensified reactions of 8-OHdG and HNE, as well as reduced expression of SOD. Islet volume density of beta cells and total beta-cell mass in the pancreas from diabetic patients were reduced by 22% (p < 0.001) and 30 % (p < 0.05). Islet volume density and total mass of (pro)insulin mRNA-positive cells were similarly reduced in diabetic patients by 22% (p < 0.001) and 39 % (p < 0.05), respectively. Islet volume density of A cells was increased by 20 % (p < 0.001) but total mass did not change. There were no changes in volume densities of islet, D and PP cells. Reduced beta-cell volume density correlated with increased positive staining of 8-OHdG.Conclusion/interpretation. Japanese Type II diabetic patients show a reduction of beta-cell mass and evidence of increased oxidative stress-related tissue damage that is correlated with the extent of the beta-cell lesions.