Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis
Dysfunction of Persisting β Cells Is a Key Feature of Early Type 2 Diabetes Pathogenesis
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DOI：
10.1016/j.celrep.2020.03.033
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发表时间：
2020-04-07
期刊：
影响因子：
8.8
通讯作者：
Speier, Stephan
中科院分区：
文献类型：
--
作者：
Cohrs, Christian M.;Panzer, Julia K.;Speier, Stephan
2型糖尿病的特征在于外周胰岛素抵抗和胰岛β细胞的胰岛素释放不足。但是，B细胞功能障碍和质量损失对于胰岛素水平降低在2型糖尿病发病机制中的作用和顺序尚不清楚。在这里，我们利用新鲜的胰腺标本从代谢表型手术患者使用原位组织切片技术。该方法允许评估代谢分层个体的胰腺样品内的β细胞体积和功能。我们发现，在糖尿病前期、葡萄糖耐受受损受试者的组织中，β细胞体积不变，但功能显著恶化，表现出基础释放增加和第一时相胰岛素分泌丧失。在2型糖尿病患者中，持续β细胞体积内的功能进一步下降。这些结果表明，持续β细胞功能障碍是2型糖尿病早期发展和进展的关键因素，是糖尿病预防和治疗的主要目标。
Type 2 diabetes is characterized by peripheral insulin resistance and insufficient insulin release from pancreatic islet beta cells. However, the role and sequence of b cell dysfunction and mass loss for reduced insulin levels in type 2 diabetes pathogenesis are unclear. Here, we exploit freshly explanted pancreas specimens from metabolically phenotyped surgical patients using an in situ tissue slice technology. This approach allows assessment of beta cell volume and function within pancreas samples of metabolically stratified individuals. We show that, in tissue of pre-diabetic, impaired glucose-tolerant subjects, beta cell volume is unchanged, but function significantly deteriorates, exhibiting increased basal release and loss of first-phase insulin secretion. In individuals with type 2 diabetes, function within the sustained beta cell volume further declines. These results indicate that dysfunction of persisting beta cells is a key factor in the early development and progression of type 2 diabetes, representing a major target for diabetes prevention and therapy.