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补充生物素饮食对小鼠胰岛β细胞质量扩张和葡萄糖诱导的电活动的影响。

Impact of biotin supplemented diet on mouse pancreatic islet β-cell mass expansion and glucose induced electrical activity.

机构信息

Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Circuito Interior S/N, Universidad Nacional Autónoma de México, C.U., CDMXLaboratorio de sinapsis eléctricas. Departamento de Biología Celular y , México.

Human Genetics Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.

出版信息

Islets. 2022 Dec 31;14(1):149-163. doi: 10.1080/19382014.2022.2091886.

DOI:10.1080/19382014.2022.2091886
PMID:35758027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9733685/
Abstract

Biotin supplemented diet (BSD) is known to enhance β-cell replication and insulin secretion in mice. Here, we first describe BSD impact on the islet β-cell membrane potential (Vm) and glucose-induced electrical activity. BALB/c female mice (n ≥ 20) were fed for nine weeks after weaning with a control diet (CD) or a BSD (100X). In both groups, islet area was compared in pancreatic sections incubated with anti-insulin and anti-glucagon antibodies; Vm was recorded in micro dissected islet β-cells during perfusion with saline solutions containing 2.8, 5.0, 7.5-, or 11.0 mM glucose. BSD increased the islet and β-cell area compared with CD. In islet β-cells of the BSD group, a larger ΔVm/Δ[glucose] was found at sub-stimulatory glucose concentrations and the threshold glucose concentration for generation of action potentials (APs) was increased by 1.23 mM. Moreover, at 11.0 mM glucose, a significant decrease was found in AP amplitude, frequency, ascending and descending slopes as well as in the calculated net charge influx and efflux of islet β-cells from BSD compared to the CD group, without changes in slow Vm oscillation parameters. A pharmacological dose of biotin in mice increases islet insulin cell mass, shifts islet β-cell intracellular electrical activity dose response curve toward higher glucose concentrations, very likely by increasing K conductance, and decreases voltage gated Ca and K conductance at stimulatory glucose concentrations.

摘要

生物素补充饮食(BSD)已知可增强小鼠胰岛β细胞的复制和胰岛素分泌。在这里,我们首先描述 BSD 对胰岛β细胞膜电位(Vm)和葡萄糖诱导的电活性的影响。断奶后,雌性 BALB/c 小鼠(n≥20)用对照饮食(CD)或 BSD(100X)喂养九周。在两组中,用抗胰岛素和抗胰高血糖素抗体孵育胰腺切片,比较胰岛面积;在含有 2.8、5.0、7.5 或 11.0 mM 葡萄糖的盐溶液灌流期间,记录微分离的胰岛β细胞中的 Vm。与 CD 相比,BSD 增加了胰岛和β细胞面积。在 BSD 组的胰岛β细胞中,在亚刺激葡萄糖浓度下发现更大的 ΔVm/Δ[glucose],并且产生动作电位(AP)的阈值葡萄糖浓度增加了 1.23 mM。此外,在 11.0 mM 葡萄糖下,与 CD 组相比,BSD 组胰岛β细胞的 AP 幅度、频率、上升和下降斜率以及计算的净电荷流入和流出显著降低,而缓慢 Vm 振荡参数没有变化。在小鼠中,生物素的药理剂量增加胰岛胰岛素细胞质量,将胰岛β细胞细胞内电活动剂量反应曲线向更高的葡萄糖浓度转移,很可能通过增加 K 电导来实现,并降低刺激葡萄糖浓度下的电压门控 Ca 和 K 电导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/d7b17bb2fefc/KISL_A_2091886_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/71c5ba845c2f/KISL_A_2091886_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/9636bcca4511/KISL_A_2091886_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/02973514bace/KISL_A_2091886_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/9407c3595b54/KISL_A_2091886_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/d7b17bb2fefc/KISL_A_2091886_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/71c5ba845c2f/KISL_A_2091886_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/9636bcca4511/KISL_A_2091886_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/02973514bace/KISL_A_2091886_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/9407c3595b54/KISL_A_2091886_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc87/9733685/d7b17bb2fefc/KISL_A_2091886_F0004_B.jpg

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