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首页> 外文期刊>American Journal of Physiology >Postnatal development of the endocrine pancreas in mice lacking functional GABAB receptors
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Postnatal development of the endocrine pancreas in mice lacking functional GABAB receptors

机译：缺乏功能性GABAB受体的小鼠的内分泌胰腺的产后发育

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Adult mice lacking functional GABAB receptors (GABAB1KO) have glucose metabolism alterations. Since GABAB receptors (GABABRs) are expressed in progenitor cells, we evaluated islet development in GABAB1KO mice. Postnatal day 4 (PND4) and adult, male and female, GABAB1KO, and wild-type littermates (WT) were weighed and euthanized, and serum insulin and glucagon was measured. Pancreatic glucagon and insulin content were assessed, and pancreas insulin, glucagon, PCNA, and GAD65/67 were determined by immunohistochemistry. RNA from PND4 pancreata and adult isolated islets was obtained, and Ins1, Ins2, Gcg, Sst, Ppy, Nes, Pdx1, and Gad1 transcription levels were determined by quantitative PCR. The main results were as follows: 1) insulin content was increased in PND4 GABAB1KO females and in both sexes in adult GABAB1KOs; 2) GABAB1KO females had more clusters (500 μm2) and less islets than WT females; 3) cluster proliferation was decreased at PND4 and increased in adult GABAB1KO mice; 4) increased β-area at the expense of the α-cell area was present in GABAB1KO islets; 5) Ins2, Sst, and Ppy transcription were decreased in PND4 GABAB1KO pancreata, adult GABAB1KO female islets showed increased Ins1, Ins2, and Sst expression, Pdx1 was increased in male and female GABAB1KO islets; and 6) GAD65/67 was increased in adult GABAB1KO pancreata. We demonstrate that several islet parameters are altered in GABAB1KO mice, further pinpointing the importance of GABABRs in islet physiology. Some changes persist from neonatal ages to adulthood (e.g., insulin content in GABAB1KO females), whereas other features are differentially regulated according to age (e.g., Ins2 was reduced in PND4, whereas it was upregulated in adult GABAB1KO females).
机译：缺乏功能性GABAB受体（GABAB1KO）的成年小鼠具有葡萄糖代谢改变。由于GABAB受体（GABABRs）在祖细胞中表达，我们评估了GABAB1KO小鼠的胰岛发育。出生后第4天（PND4）和成年，雄性和雌性，GABAB1KO和野生型同窝动物（WT）称重并安乐死，并测量血清胰岛素和胰高血糖素。评估胰高血糖素和胰岛素含量，并通过免疫组织化学测定胰腺胰岛素，胰高血糖素，PCNA和GAD65 / 67。获得了来自PND4胰腺和成年分离的胰岛的RNA，并通过定量PCR测定了Ins1，Ins2，Gcg，Sst，Ppy，Nes，Pdx1和Gad1的转录水平。主要结果如下：1）成年GABAB1KOs的PND4 GABAB1KO雌性和雌雄中胰岛素含量均增加; 2）与野生型雌性相比，GABAB1KO雌性具有更多的簇（<500μm2）和更少的胰岛; 3）成年GABAB1KO小鼠的PND4团簇增殖减少而增加; 4）在GABAB1KO胰岛中，以α细胞面积为代价增加了β面积; 5）在PND4 GABAB1KO胰腺中Ins2，Sst和Ppy转录降低，成年GABAB1KO雌性胰岛显示Ins1，Ins2和Sst表达增加，在男性和女性GABAB1KO胰岛中Pdx1增加; 6）成年GABAB1KO胰腺中GAD65 / 67升高。我们证明了几个胰岛参数在GABAB1KO小鼠中发生了改变，进一步指出了GABABRs在胰岛生理中的重要性。从新生儿到成年，某些变化持续存在（例如，GABA B1KO女性中的胰岛素含量），而其他功能则根据年龄进行差异调节（例如，PNS4中的Ins2减少，而成年GABA B1KO女性中的Ins2上调）。

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