Objective

As diabetes develops, marked reductions of insulin secretion are associated with very modest elevations of glucose. We wondered if these glucose changes disrupt beta cell differentiation enough to account for the altered function.

Methods

Rats were subjected to 90% partial pancreatectomies and those with only mild glucose elevations 4 weeks or 10 weeks after surgery had major alterations of gene expression in their islets as determined by RNAseq.

Results

Changes associated with glucose toxicity demonstrated that many of the critical genes responsible for insulin secretion were downregulated while the expression of normally suppressed genes increased. Also, there were marked changes in genes associated with replication, aging, senescence, stress, inflammation, and increased expression of genes controlling both class I and II MHC antigens.

Conclusions

These findings suggest that mild glucose elevations in the early stages of diabetes lead to phenotypic changes that adversely affect beta cell function, growth, and vulnerability.

中文翻译：

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轻度高血糖导致β细胞身份发生变化：对功能、生长和脆弱性的影响。

 客观的

随着糖尿病的发展，胰岛素分泌的显着减少与血糖的适度升高有关。我们想知道这些葡萄糖变化是否足以扰乱β细胞分化以解释功能的改变。

 方法

90% 的大鼠接受了部分胰腺切除术，根据 RNAseq 测定，那些在术后 4 周或 10 周仅出现轻度血糖升高的大鼠，其胰岛中的基因表达发生了重大变化。

 结果

与葡萄糖毒性相关的变化表明，许多负责胰岛素分泌的关键基因被下调，而通常被抑制的基因的表达却增加。此外，与复制、衰老、衰老、应激、炎症相关的基因也发生了显着变化，并且控制 I 类和 II 类 MHC 抗原的基因表达增加。

 结论

这些发现表明，糖尿病早期阶段的轻度葡萄糖升高会导致表型变化，对 β 细胞功能、生长和脆弱性产生不利影响。