期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1866, 期 3, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2019.165613
关键词
Apolipoprotein A-I; High density lipoprotein; Insulin granules; Type 2 diabetes; Beta cell
资金
- Swedish Research council [K2014-54X-22426-01-3, 2016-02124, 2009-1039]
- Swedish Diabetes Foundation
- Albert PAhlsson Foundation
- NovoNordisk Foundation
- Vinnova (Sweden's Innovation Agency) [2015-01549]
- Royal Physiographic Society in Lund
- krapperup Foundation
- Carl Tesdorpfs foundation
- Diabetes Research and Wellness Foundation Sweden
- Swedish Foundation for Strategic Research [IRC15-0067]
- Vinnova [2015-01549] Funding Source: Vinnova
- Swedish Research Council [2016-02124] Funding Source: Swedish Research Council
The increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion. INS-1E rat clonal beta cells as well as isolated murine islets were used to study the effect of ApoA-I on responsiveness of the beta cells to high glucose challenge. Confocal and transmission electron microscopy were used to dissect ApoA-I mechanisms of action. Chemical endocytosis blockers were used to understand the role of ApoA-I internalization in mediating its positive effect. Pre-incubation of beta cells and isolated murine islets with ApoA-I augmented glucose stimulated insulin secretion. This effect appeared to be due to an increased reservoir of insulin granules at the cell membrane, as confirmed by confocal and transmission electron microscopy. Moreover, ApoA-I induced pancreatic and duo-denal homeobox 1 (PDX1) shuttling from the cytoplasm to the nucleus, with the subsequent increase in the proinsulin processing enzyme protein convertase 1 (PC1/3). Finally, the blockade of ApoA-I endocytosis in beta cells resulted in a loss of ApoA-I positive action on insulin secretion. The proposed mechanisms of the phenomenon here described include ApoA-I internalization into beta cells, PDX1 nuclear translocation, and increased levels of proinsulin processing enzymes. Altogether, these events lead to an increased number of insulin granules.
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。
推荐
暂无数据