Effects of Glucocorticoid Treatment on β- and α-Cell Mass in Japanese Adults With and Without Diabetes
Effects of Glucocorticoid Treatment on β- and α-Cell Mass in Japanese Adults With and Without Diabetes
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DOI：
10.2337/db15-0151
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发表时间：
2015-08-01
期刊：
影响因子：
7.7
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
--
作者：
Sato, Seiji;Saisho, Yoshifumi;Itoh, Hiroshi
本研究的目的是1）阐明面对糖皮质激素（GC）诱导的胰岛素抵抗时β细胞的再生能力，2）阐明GC诱导的人类糖尿病中β细胞和α细胞质量的变化。我们从100例日本尸检病例中获得胰腺。根据受试者死前是否接受过GC治疗以及是否患有糖尿病对病例进行分类。定量β细胞面积分数（%BCA）和α细胞面积（%ACA），并评价与GC治疗的关系。因此，在无糖尿病的病例受试者中，接受和未接受GC治疗的病例受试者之间的%BCA无显著差异（1.66 +/- 1.05% vs. 1.21 +/-0.59%，P = 0.13）。%ACA在两组之间也没有显著差异。在患有2型糖尿病的病例受试者中，与不患有糖尿病的对照受试者相比，%BCA和%ACA均显著降低;然而，在患有GC诱导的糖尿病的病例受试者中，%BCA和%ACA均未显著降低。死亡前测量的%BCA和HbA（1c）之间存在显著负相关;然而，在接受GC治疗的病例受试者中，这种关系减弱。总之，目前的研究表明，β-和α-细胞质量在很大程度上保持不变，面对GC诱导的胰岛素抵抗在日本个人，这意味着有限的能力β-细胞再生成人。在患有GC诱导的糖尿病的病例受试者中不存在明显的β细胞缺陷表明GC诱导的糖尿病主要由胰岛素抵抗和/或β细胞功能障碍引起，但不一定是β细胞质量缺陷。
The aim of this study was 1) to clarify beta-cell regenerative capacity in the face of glucocorticoid (GC)-induced insulin resistance and 2) to clarify the change in beta- and alpha-cell mass in GC-induced diabetes in humans. We obtained the pancreases from 100 Japanese autopsy case subjects. The case subjects were classified according to whether or not they had received GC therapy before death and the presence or absence of diabetes. Fractional beta-cell area (%BCA) and alpha-cell area (%ACA) were quantified, and the relationship with GC therapy was evaluated. As a result, in case subjects without diabetes, there was no significant difference in %BCA between case subjects with and without GC therapy (1.66 +/- 1.05% vs. 1.21 +/- 0.59%, P = 0.13). %ACA was also not significantly different between the two groups. In case subjects with type 2 diabetes, %BCA and %ACA were both significantly reduced compared with control subjects without diabetes; however, neither %BCA nor %ACA was significantly decreased in case subjects with GC-induced diabetes. There was a significant negative correlation between %BCA and HbA(1c) measured before death; however, this relationship was attenuated in case subjects with GC therapy. In conclusion, the current study suggests that beta- and alpha-cell mass remain largely unchanged in the face of GC-induced insulin resistance in Japanese individuals, implying limited capacity of beta-cell regeneration in adult humans. The absence of apparent beta-cell deficit in case subjects with GC-induced diabetes suggests that GC-induced diabetes is mainly caused by insulin resistance and/or beta-cell dysfunction, but not necessarily a deficit of beta-cell mass.