Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice.
Normal β-Cell Glut2 Expression Is not Required for Regulating Glucose-Stimulated Insulin Secretion and Systemic Glucose Homeostasis in Mice.
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DOI：
10.3390/biom13030540
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发表时间：
2023-03-16
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
目的：葡萄糖转运蛋白2（glucose transporter 2，GLUT 2）在小鼠胰腺β细胞、肠、肝、肾中均有表达。尽管GLUT 2被认为是胰岛素分泌的主要调节因子，但β细胞Glut 2对葡萄糖刺激的胰岛素分泌和全身葡萄糖稳态的体内作用尚不明确。因此，本研究的主要目的是确定β细胞Glut 2在调节小鼠胰岛素分泌和血糖水平中的作用。研究方法：通过将Glut 2LoxP/LoxP小鼠与Ins 1CreERT 2小鼠品系杂交并使用Cre-Lox重组技术，我们产生了可以在期望的时间特异性地在β细胞中敲低Glut 2的小鼠（β-Glut 2 KD）。我们测量了β-Glut 2 KD小鼠的空腹血糖水平、葡萄糖耐量和葡萄糖刺激的胰岛素分泌。我们使用qRT-PCR和免疫荧光来验证β-Glut 2 KD小鼠中β-细胞Glut 2的缺陷。结果：我们报道了雄性和雌性β-Glut 2 KD小鼠均具有正常的葡萄糖刺激的胰岛素分泌。此外，β-Glut 2 KD小鼠表现出正常的空腹血糖水平和葡萄糖耐量。β-Glut 2 KD小鼠胰岛中GLUT 1上调。结论：我们的研究结果表明，正常的β细胞Glut 2表达对于调节小鼠葡萄糖刺激的胰岛素分泌和全身葡萄糖稳态不是必需的。因此，目前认为β细胞GLUT 2在调节胰岛素分泌和血糖水平中的作用需要重新校准。这将允许有机会确定其他β细胞葡萄糖转运蛋白或其正常表达可能是介导葡萄糖刺激的胰岛素分泌所必需的因子的贡献。
Objective: Glucose transporter 2 (GLUT2) is expressed in the pancreatic β-cell, intestine, liver, and kidney in mice. Although GLUT2 is considered as a major regulator of insulin secretion, in vivo contribution of β-cell Glut2 to glucose-stimulated insulin secretion and systemic glucose homeostasis is undefined. Therefore, the main objective of this study is to determine the role of β-cell Glut2 in regulating insulin secretion and blood glucose levels in mice. Methods: We produced mice in which we can knock down Glut2 at a desired time specifically in β-cells (β-Glut2 KD) by crossing Glut2LoxP/LoxP mice with Ins1CreERT2 mouse strain and using the Cre-Lox recombination technique. We measured fasting blood glucose levels, glucose tolerance, and glucose-stimulated insulin secretion in the β-Glut2 KD mice. We used qRT-PCR and immunofluorescence to validate the deficiency of β-cell Glut2 in β-Glut2 KD mice. Results: We report that both male and female β-Glut2 KD mice have normal glucose-stimulated insulin secretion. Moreover, the β-Glut2 KD mice exhibit normal fasting blood glucose levels and glucose tolerance. The β-Glut2 KD mice have upregulated GLUT1 in islets. Conclusions: Our findings demonstrate that normal β-cell Glut2 expression is not essential for regulating glucose-stimulated insulin secretion and systemic glucose homeostasis in mice. Therefore, the currently assumed role of β-cell GLUT2 in regulating insulin secretion and blood glucose levels needs to be recalibrated. This will allow an opportunity to determine the contribution of other β-cell glucose transporters or factors whose normal expression may be necessary for mediating glucose stimulated insulin secretion.
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影响因子：
8.2
作者：
Cordeiro, Leticia Maria de Souza;Bainbridge, Lauren;Devisetty, Nagavardhini;McDougal, David H.;Peters, Dorien J. M.;Chhabra, Kavaljit H.
通讯作者：
Chhabra, Kavaljit H.
影响因子：
8.2
作者：
Sansbury, F. H.;Flanagan, S. E.;Hattersley, A. T.
通讯作者：
Hattersley, A. T.
影响因子：
1.2
作者：
Zmuda, Erik J.;Powell, Catherine A.;Hai, Tsonwin
通讯作者：
Hai, Tsonwin
影响因子：
4.8
作者：
Thorens, B;Guillam, MT;Jaquet, M
通讯作者：
Jaquet, M
影响因子：
8.1
作者：
Chae H;Augustin R;Gatineau E;Mayoux E;Bensellam M;Antoine N;Khattab F;Lai BK;Brusa D;Stierstorfer B;Klein H;Singh B;Ruiz L;Pieper M;Mark M;Herrera PL;Gribble FM;Reimann F;Wojtusciszyn A;Broca C;Rita N;Piemonti L;Gilon P
通讯作者：
Gilon P