Fertility and pregnancy-associated ß-cell proliferation in mice deficient in proglucagon-derived peptides.
Fertility and pregnancy-associated ß-cell proliferation in mice deficient in proglucagon-derived peptides.
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DOI：
10.1371/journal.pone.0043745
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hayashi Y
中科院分区：
文献类型：
--
作者：
Sugiyama C;Yamamoto M;Kotani T;Kikkawa F;Murata Y;Hayashi Y
由胰高血糖素基因（Gcg）编码的胰高血糖素原是几种肽激素的前体，包括胰高血糖素和胰高血糖素样肽1（GLP-1）。胰高血糖素刺激肝糖原分解和糖原合成，而GLP-1刺激胰岛素分泌以降低血糖，并且还支持胰岛细胞增殖和保护免于凋亡刺激。妊娠是胰岛功能变化的强烈诱导剂，然而胰高血糖素原衍生肽在妊娠中的作用仅部分了解。在本研究中，我们分析了纯合子胰高血糖素-绿色荧光蛋白（gfp）基因敲入小鼠（Gcggfp/gfp）的生育力和妊娠相关变化，这些小鼠缺乏来自胰高血糖素原的所有肽。雌性Gcggfp/gfp小鼠可以交付和提高Gcggfp/gfp幼崽断奶和Gcggfp/gfp幼崽从Gcggfp/gfp母鼠是可行的和可育的。在Gcgfp/gfp小鼠和对照小鼠中，妊娠诱导了β-细胞增殖。然而，妊娠Gcggfp/gfp雌性动物的血清胰岛素水平低于自由采食下的对照妊娠雌性动物，妊娠Gcggfp/gfp雌性动物的血糖水平在妊娠第12天后较高。Gcggfp/gfp雌性的妊娠率降低，产仔数减少。Gcggfp/gfp雌性的繁殖成功率显着降低，并且没有通过繁殖经验得到改善。总之，胰高血糖素原衍生的肽不是妊娠相关的胰岛β细胞增殖所需的，然而，是调节血糖水平和正常生殖能力所需的。Gcggfp/gfp小鼠可作为一种新的模型来分析妊娠晚期轻度高血糖的影响。
Proglucagon, which is encoded by the glucagon gene (Gcg), is the precursor of several peptide hormones, including glucagon and glucagon-like peptide 1 (GLP-1). Whereas glucagon stimulates hepatic glycogenolysis and gluconeogenesis, GLP-1 stimulates insulin secretion to lower blood glucose and also supports ß-cell proliferation and protection from apoptotic stimuli. Pregnancy is a strong inducer of change in islet function, however the roles of proglucagon-derived peptides in pregnancy are only partially understood. In the present study, we analyzed fertility and pregnancy-associated changes in homozygous glucagon-green fluorescent protein (gfp) knock-in mice (Gcggfp/gfp), which lack all the peptides derived from proglucagon. Female Gcggfp/gfp mice could deliver and raise Gcggfp/gfp pups to weaning and Gcggfp/gfp pups from Gcggfp/gfp dams were viable and fertile. Pregnancy induced ß-cell proliferation in Gcggfp/gfp mice as well as in control mice. However, serum insulin levels in pregnant Gcggfp/gfp females were lower than those in control pregnant females under ad libitum feeding, and blood glucose levels in pregnant Gcggfp/gfp females were higher after gestational day 12. Gcggfp/gfp females showed a decreased pregnancy rate and smaller litter size. The rate of successful breeding was significantly lower in Gcggfp/gfp females and was not improved by experience of breeding. Taken together, proglucagon-derived peptides are not required for pregnancy-associated ß-cell proliferation, however, are required for regulation of blood glucose levels and normal reproductive capacity. Gcggfp/gfp mice may serve as a novel model to analyze the effect of mild hyperglycemia during late gestational periods.
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影响因子：
8.2
作者：
Schraenen, A.;Lemaire, K.;de Faudeur, G.;Hendrickx, N.;Granvik, M.;Van Lommel, L.;Mallet, J.;Vodjdani, G.;Gilon, P.;Binart, N.;in't Veld, P.;Schuit, F.
通讯作者：
Schuit, F.
影响因子：
8.2
作者：
Butler, A. E.;Cao-Minh, L.;Galasso, R.;Rizza, R. A.;Corradin, A.;Cobelli, C.;Butler, P. C.
通讯作者：
Butler, P. C.
影响因子：
7.7
作者：
Lee Y;Wang MY;Du XQ;Charron MJ;Unger RH
通讯作者：
Unger RH
影响因子：
4.8
作者：
Dey, A;Lipkind, GM;Steiner, DF
通讯作者：
Steiner, DF
影响因子：
3.7
作者：
Mao P;Meshul CK;Thuillier P;Goldberg NR;Reddy PH
通讯作者：
Reddy PH