Distinct Roles of β-Cell Mass and Function During Type 1 Diabetes Onset and Remission
Distinct Roles of β-Cell Mass and Function During Type 1 Diabetes Onset and Remission
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DOI：
10.2337/db14-1055
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发表时间：
2015-06-01
期刊：
影响因子：
7.7
通讯作者：
Speier, Stephan
中科院分区：
文献类型：
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作者：
Chmelova, Helena;Cohrs, Christian M.;Speier, Stephan
1型糖尿病（T1D）在发病时通过免疫干预的治愈取决于内源性β细胞的胰岛素分泌的恢复。然而，对自身免疫攻击消融后β细胞质量和功能恢复的潜力知之甚少。使用纵向体内成像方法，我们展示了β细胞的功能状态和质量如何适应T1D的发作和缓解。我们证明，浸润减少发病前的β细胞质量，并与新兴的高血糖症，影响β细胞功能。免疫干预后，持续的高血糖阻止功能恢复，但促进小鼠胰岛中β细胞质量增加。当血糖水平恢复到正常水平时，β细胞群扩增停止，随后葡萄糖耐量与β细胞功能一起恢复。与小鼠胰岛相似，人胰岛在短暂高血糖时表现出细胞耗竭和恢复。然而，高血糖对人胰岛质量增加的影响是轻微和短暂的。我们的数据表明，在T1D发作和缓解期间，β细胞的功能衰竭和恢复起着重要作用。因此，这些发现支持T1D患者的早期干预治疗。
Cure of type 1 diabetes (T1D) by immune intervention at disease onset depends on the restoration of insulin secretion by endogenous beta-cells. However, little is known about the potential of beta-cell mass and function to recover after autoimmune attack ablation. Using a longitudinal in vivo imaging approach, we show how functional status and mass of beta-cells adapt in response to the onset and remission of T1D. We demonstrate that infiltration reduces beta-cell mass prior to onset and, together with emerging hyperglycemia, affects beta-cell function. After immune intervention, persisting hyperglycemia prevents functional recovery but promotes beta-cell mass increase in mouse islets. When blood glucose levels return to normoglycemia beta-cell mass expansion stops, and subsequently glucose tolerance recovers in combination with beta-cell function. Similar to mouse islets, human islets exhibit cell exhaustion and recovery in response to transient hyperglycemia. However, the effect of hyperglycemia on human islet mass increase is minor and transient. Our data demonstrate a major role of functional exhaustion and recovery of beta-cells during T1D onset and remission. Therefore, these findings support early intervention therapy for individuals with T1D.