Glucagon-producing cells are increased in Mas-deficient mice.
Glucagon-producing cells are increased in Mas-deficient mice.
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DOI：
10.1530/ec-16-0098
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发表时间：
2017-01
影响因子：
2.9
通讯作者：
Santos RA
中科院分区：
文献类型：
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作者：
Felix Braga J;Ravizzoni Dartora D;Alenina N;Bader M;Santos RA
已经显示血管紧张素（1-7）（Ang（1-7））产生与葡萄糖稳态相关的几种作用。本研究旨在探讨Ang（1-7）基因缺失对胰高血糖素分泌细胞的影响。C57 BL 6/N Mas−/−小鼠胰腺α细胞显著增加，（细胞数：146 ± 21 vs WT中67 ± 8; P < 0.001）和每个胰岛的百分比（17.9 ± 0.91 vs WT中12.3 ± 0.9%; P < 0.0001），随后β细胞百分比降低（82.1 ± 0.91 vs WT中87.7 ± 0.9%; P < 0.0001）。因此，C57 BL 6/N Mas−/−小鼠中胰高血糖素血浆水平升高（WT中为516.7 ± 36.35 vs 390.8 ± 56.45 pg/mL; P < 0.05），胰岛素血浆水平降低（WT中为0.25 ± 0.01 vs 0.31 ± 56.45 pg/mL; P = 0.02）。为了排除背景相关表型的可能性，我们测定了FVB/N Mas−/−小鼠中胰高血糖素产生细胞的数量。与C57 BL 6/N Mas−/−小鼠中的观察结果一致，这些小鼠中胰腺α细胞的数量和百分比也显著增加（α细胞数量：260 ± 22 vs WT中的156 ± 12，P < 0.001;每个胰岛的百分比：16 ± 0.8 vs WT中的10 ± 0.5%，P < 0.0001）。这些结果表明Mas对胰高血糖素的产生具有先前意想不到的作用。
It has been shown that angiotensin(1–7) (Ang(1–7)) produces several effects related to glucose homeostasis. In this study, we aimed to investigate the effects of genetic deletion of Ang(1–7), the GPCR Mas, on the glucagon-producing cells. C57BL6/N Mas−/− mice presented a significant and marked increase in pancreatic α-cells (number of cells: 146 ± 21 vs 67 ± 8 in WT; P < 0.001) and the percentage per islet (17.9 ± 0.91 vs 12.3 ± 0.9% in WT; P < 0.0001) with subsequent reduction of β-cells percentage (82.1 ± 0.91 vs 87.7 ± 0.9% in WT; P < 0.0001). Accordingly, glucagon plasma levels were increased (516.7 ± 36.35 vs 390.8 ± 56.45 pg/mL in WT; P < 0.05) and insulin plasma levels were decreased in C57BL6/N Mas−/− mice (0.25 ± 0.01 vs 0.31 ± 56.45 pg/mL in WT; P = 0.02). In order to eliminate the possibility of a background-related phenotype, we determined the number of glucagon-producing cells in FVB/N Mas−/− mice. In keeping with the observations in C57BL6/N Mas−/− mice, the number and percentage of pancreatic α-cells were also significantly increased in these mice (number of α-cells: 260 ± 22 vs 156 ± 12 in WT, P < 0.001; percentage per islet: 16 ± 0.8 vs 10 ± 0.5% in WT, P < 0.0001). These results suggest that Mas has a previously unexpected role on the pancreatic glucagon production.