Vitamin A deficiency causes islet dysfunction by inducing islet stellate cell activation via cellular retinol binding protein 1
Vitamin A deficiency causes islet dysfunction by inducing islet stellate cell activation via cellular retinol binding protein 1
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维生素 A 缺乏通过细胞视黄醇结合蛋白 1 诱导胰岛星状细胞活化，从而导致胰岛功能障碍
DOI：
10.7150/ijbs.37861
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发表时间：
2020-01
影响因子：
9.2
通讯作者：
Zilin Sun
中科院分区：
文献类型：
--
作者：
Yunting Zhou;Junming Zhou;Bo Sun;Wei Xu;Ming Zhong;Yumin Li;Cong He;Yang Chen;Xiaohang Wang;Peter B. Jones;Zilin Sun
Background: Vitamin A (VA) plays an essential role in pancreatic homeostasis. Islet stellate cells (ISCs) are VA-storing cells in pancreatic islets. Herein, we have investigated the effect of VA on glucose homeostasis trough regulation of ISCs function in dietary VA deficiency model mice. Methods: Male C57BL/6 mice were randomly fed a VA-sufficient, a VA-deficient (VAD) or a VAD-rescued diet. Glucose metabolism was assessed by glucose tolerance tests and immunohistochemistry. ISCs activation degree was evaluated by immunofluorescence, quantitative PCR and western blotting in both, retinol-treated cultured ISCs and model mice. Changes in ISCs phenotype and their effect on islets were assessed by lentiviral transduction and enzyme-linked immunosorbent assays in a co-culture system. Results: VAD mice showed irregular shaped islet, glucose intolerance, islet size distribution excursions, and upregulated expression of α-smooth muscle actin (α-SMA, marker of ISCs activation). Reintroduction of dietary VA restored pancreatic VA levels, endocrine hormone profiles, and inhibited ISCs activation. Incubation with retinol increased the expression of VA signaling factors in ISCs, including cellular retinol binding protein 1 (CRBP1). The knockdown of CRBP1 maintained the quiescent ISCs phenotype and reduced the damage of activated ISCs on islet function. Conclusions: VA deficiency reduced islet function by activating ISCs in VAD mice. Restoring ISCs quiescence via CRBP1 inhibition could reverse the impairment of islet function caused by activated ISCs exposure.
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DOI：
10.1073/pnas.1008859107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Kane, Maureen A.;Folias, Alexandra E.;Napoli, Joseph L.
通讯作者：
Napoli, Joseph L.
影响因子：
3.7
作者：
L. Tannous-Khuri;D. Talmage
通讯作者：
L. Tannous-Khuri;D. Talmage
影响因子：
4.3
作者：
Zhou Y;Hu Q;Chen F;Zhang J;Guo J;Wang H;Gu J;Ma L;Ho G
通讯作者：
Ho G
影响因子：
2.2
作者：
Kim A;Miller K;Jo J;Kilimnik G;Wojcik P;Hara M
通讯作者：
Hara M
影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G