Mestrado em Nutrição, Alimentos e Metabolismo, Faculdade de Nutrição, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil.
Departamento de Alimentos e Nutrição, Faculdade de Nutrição, Universidade Federal de Mato Grosso (UFMT), Avenida Fernando Correa da Costa, 2367 Bairro Boa Esperança, Cuiabá, MT, 78060-900, Brazil.
Eur J Nutr. 2020 Dec;59(8):3565-3579. doi: 10.1007/s00394-020-02192-6. Epub 2020 Feb 19.
In the present study, we investigated whether intra-islet GLP-1 production and its modulation have a role in apoptosis, proliferation or neogenesis that is compromised by protein restriction during the foetal and suckling periods.
Exendin-4, a GLP-1 receptor agonist (treated groups), or saline (non-treated groups) was intraperitoneally administered for 15 days from 75 to 90 days of age in female adult rats consisting of offspring born to and suckled by mothers fed a control diet (control groups) and who had the same diet until 90 days of age or offspring born to and suckled by mothers fed a low-protein diet and who were fed the control diet after weaning until 90 days of age (protein-restricted group).
The β-cell mass was lower in the protein-restricted groups than in the control groups. Exendin-4 increased β-cell mass, regardless of the mother's protein intake. The colocalization of GLP-1/glucagon was higher in the protein-restricted rats than in control rats in both the exendin-4-treated and non-treated groups. The frequency of cleaved caspase-3-labelled cells was higher in the non-treated protein-restricted group than in the non-treated control group and was similar in the treated protein-restricted and treated control groups. Regardless of treatment with exendin-4, Ki67-labelled cell frequency and β-catenin/DAPI colocalization were elevated in the protein-restricted groups. Exendin-4 increased the area of endocrine cell clusters and β-catenin/DAPI and FoxO1/DAPI colocalization regardless of the mother's protein intake.
Protein restriction in early life increased intra-islet GLP-1 production and β-cell proliferation, possibly mediated by the β-catenin pathway.
在本研究中，我们研究了胰岛内 GLP-1 的产生及其调节作用是否在凋亡、增殖或新生中起作用，而这些作用在胎儿和哺乳期期间受到蛋白质限制的影响。
在 75 至 90 日龄的雌性成年大鼠中，从第 75 天到第 90 天，每天通过腹腔内注射给予 Exendin-4（GLP-1 受体激动剂，治疗组）或生理盐水（非治疗组），这些大鼠的后代由接受对照饮食喂养的母亲所生并哺乳（对照组），且在 90 日龄前也接受相同的饮食，或者由接受低蛋白饮食喂养的母亲所生并哺乳，在断奶后接受对照饮食喂养至 90 日龄（蛋白质限制组）。
蛋白质限制组的β细胞质量低于对照组。无论母亲的蛋白质摄入量如何，Exendin-4 均可增加β细胞质量。在 Exendin-4 治疗和未治疗的蛋白质限制组大鼠中，GLP-1/胰高血糖素的共定位均高于对照组。未治疗的蛋白质限制组的 cleaved caspase-3 标记细胞的频率高于未治疗的对照组，而治疗的蛋白质限制组和治疗的对照组的频率相似。无论是否用 Exendin-4 治疗，蛋白质限制组的 Ki67 标记细胞的频率和β-catenin/DAPI 的共定位均升高。无论母亲的蛋白质摄入量如何，Exendin-4 均可增加内分泌细胞簇的面积以及β-catenin/DAPI 和 FoxO1/DAPI 的共定位。
生命早期的蛋白质限制增加了胰岛内 GLP-1 的产生和β细胞的增殖，这可能是通过β-catenin 途径介导的。
