Age-associated changes of islet endocrine cells and the effects of body mass index in Japanese.
Age-associated changes of islet endocrine cells and the effects of body mass index in Japanese.
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DOI：
10.1111/jdi.12118
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发表时间：
2014-02-12
影响因子：
3.2
通讯作者：
Yagihashi S
中科院分区：
文献类型：
--
作者：
Mizukami H;Takahashi K;Inaba W;Osonoi S;Kamata K;Tsuboi K;Yagihashi S
β细胞的生长受损和过早死亡与2型糖尿病中胰岛病理学的进展有关。然而，衰老如何影响胰岛细胞，或者糖尿病中的胰岛变化是否是衰老的增强过程，仍不清楚。我们研究了日本非糖尿病受试者胰岛结构的年龄相关变化，并探讨了变化的潜在机制。共对115例非糖尿病尸检病例进行了胰岛、β细胞和非β细胞体积密度及其质量的形态计量学分析。还检查了通过Ki 67鉴定的增殖活性，以及胰腺和十二指肠同源框（PDX）-1、细胞周期抑制剂P16和氧化应激标志物γ H2 AX的表达。随着年龄的增长，胰岛、β-细胞和非β-细胞的体积密度逐渐和边际下降，而这些成分的质量在成熟过程中增加，并在40年代后缓慢下降。胰岛密度在年轻时较高，但成熟后降低。体重指数（BMI）增加对β细胞质量增加的影响很小，但对其他变量没有影响。Ki 67阳性表达和PDX-1表达在年轻人中较高，但在成熟后较低，而P16和γ H2 AX表达在老年人中升高。成熟后，与年龄相关的β细胞质量下降是微不足道的，β细胞质量的减少可能是糖尿病的一个特定过程。在糖耐量正常的日本人中，BMI对胰岛结构的影响有限。
Impaired growth and premature death of β‐cells are implicated in the progression of islet pathology in type 2 diabetes. It remains unclear, however, how aging affects islet cells, or whether the islet change in diabetes is an augmented process of aging. We studied age‐related changes of the islet structure in Japanese non‐diabetic subjects and explored the underlying mechanism of the changes. A total of 115 non‐diabetic autopsy cases were subjected to morphometric analysis for volume densities of islets, β‐ and non‐β‐cells, as well as their masses. Proliferation activity identified by Ki67, and expressions of pancreatic and duodenal homeobox (PDX)‐1, cell cycle inhibitor P16, and oxidative stress marker γH2AX were also examined. There was a gradual and marginal decline of volume densities of islets, β‐ and non‐β‐cells with aging, while masses of these components were increased during maturation and slowly decreased after the 40s. Islet density was high in the young, but reduced after maturation. There was only a minimal influence of increased body mass index (BMI) on the increase in β‐cell mass, but not on the other variables. Ki67 positivity and PDX‐1 expressions were high in the young, but low after maturation, whereas expressions of P16 and γH2AX were elevated in the aged. Age‐associated decline of β‐cell mass is marginal after maturation, and the reduction of β‐cell mass could be a specific process in diabetes. The impact of BMI on the islet structure is limited in Japanese with normal glucose tolerance.
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DOI：
10.1038/labinvest.2010.124
发表时间：
2010-11
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.1
作者：
Gustafsson AB;Gottlieb RA
通讯作者：
Gottlieb RA
影响因子：
7.7
作者：
Meier, Juris J.;Butler, Alexandra E.;Butler, Peter C.
通讯作者：
Butler, Peter C.
影响因子：
7.7
作者：
Kawamori, D;Kajimoto, Y;Hori, M
通讯作者：
Hori, M
影响因子：
4.8
作者：
Kaneto, H;Xu, G;Weir, GC
通讯作者：
Weir, GC