4.7 Article

Gene Delivery of Manf to Beta-Cells of the Pancreatic Islets Protects NOD Mice from Type 1 Diabetes Development

期刊

BIOMOLECULES
卷 12, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/biom12101493

关键词

type 1 diabetes; AAV; Manf; gene delivery; NOD mice; beta-cells

资金

  1. VIB
  2. Biotechnology and Biological Sciences Research Council (BBSRC) through Institute Strategic Program [BBS/E/B/000C0427, BBS/E/B/000C0428]
  3. BBSRC Core Capability Grant
  4. Vetenskapsradet
  5. Swedish Diabetes Foundation
  6. Barndiabetesfonden
  7. FWO
  8. O.E. och Edla Johanssons
  9. Sederholm
  10. Magnus Bergvalls Stiftelse
  11. Ernfors Fund
  12. Nils Erik Holmstens
  13. SEB-Diabetesfonden

向作者/读者索取更多资源

This article discusses the causes and mechanisms of insulin-producing beta-cell death in type 1 diabetes. Cellular stress is found to contribute to the loss of beta-cells. By enhancing the expression of the anti-apoptotic protein Manf, the robustness of beta-cells can be improved, leading to a lower incidence of type 1 diabetes.
In type 1 diabetes, dysfunctional glucose regulation occurs due to the death of insulin-producing beta-cells in the pancreatic islets. Initiation of this process is caused by the inheritance of an adaptive immune system that is predisposed to responding to beta-cell antigens, most notably to insulin itself, coupled with unknown environmental insults priming the autoimmune reaction. While autoimmunity is a primary driver in beta-cell death, there is growing evidence that cellular stress participates in the loss of beta-cells. In the beta-cell fragility model, partial loss of islet mass requires compensatory upregulation of insulin production in the remaining islets, driving a cellular stress capable of triggering apoptosis in the remaining cells. The Glis3-Manf axis has been identified as being pivotal to the relative fragility or robustness of stressed islets, potentially operating in both type 1 and type 2 diabetes. Here, we have used an AAV-based gene delivery system to enhance the expression of the anti-apoptotic protein Manf in the beta-cells of NOD mice. Gene delivery substantially lowered the rate of diabetes development in treated mice. Manf-treated mice demonstrated minimal insulitis and superior preservation of insulin production. Our results demonstrating the therapeutic potential of Manf delivery to enhance beta-cell robustness and avert clinical diabetes.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据