Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice
Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice
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DOI：
10.1152/ajpendo.00423.2003
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发表时间：
2004-09-01
影响因子：
5.1
通讯作者：
Liu, YL
中科院分区：
文献类型：
--
作者：
Liu, JL;Coschigano, KT;Liu, YL
生长激素通过其受体（GHR）起作用，在碳水化合物代谢和促进出生后生长中起重要作用。GHR基因缺陷（GHR（-/-））小鼠表现出严重的生长迟缓和比例侏儒症。为了评估生长激素作用的生理相关性，使用GHR（-/-）小鼠来研究它们在葡萄糖代谢和胰岛功能中的表型。成年GHR（-/-）小鼠表现出血糖和胰岛素水平以及胰岛素mRNA积累的显著降低。胰腺切片的免疫组织化学分析显示，尽管胰岛的大小显着较小，但分布正常。在GHR（-/-）小鼠中发现的胰岛的平均大小仅为野生型同窝仔的三分之一。GHR（-/-）小鼠的总β细胞量减少了4.5倍，显著超过其体型的减少。胰岛质量的减少似乎与增殖和细胞生长的减少有关。GHR（-/-）小鼠在血清胰岛素水平、胰岛素反应性和肥胖方面与人类Laron综合征不同。我们的结论是，生长激素信号是必不可少的，以维持胰岛大小，刺激胰岛激素的生产，并维持正常的胰岛素敏感性和葡萄糖稳态。
Growth hormone, acting through its receptor (GHR), plays an important role in carbohydrate metabolism and in promoting postnatal growth. GHR gene-deficient (GHR(-/-)) mice exhibit severe growth retardation and proportionate dwarfism. To assess the physiological relevance of growth hormone actions, GHR(-/-) mice were used to investigate their phenotype in glucose metabolism and pancreatic islet function. Adult GHR(-/-) mice exhibited significant reductions in the levels of blood glucose and insulin, as well as insulin mRNA accumulation. Immunohistochemical analysis of pancreatic sections revealed normal distribution of the islets despite a significantly smaller size. The average size of the islets found in GHR(-/-) mice was only one-third of that in wild-type littermates. Total beta-cell mass was reduced 4.5-fold in GHR(-/-) mice, significantly more than their body size reduction. This reduction in pancreatic islet mass appears to be related to decreases in proliferation and cell growth. GHR(-/-) mice were different from the human Laron syndrome in serum insulin level, insulin responsiveness, and obesity. We conclude that growth hormone signaling is essential for maintaining pancreatic islet size, stimulating islet hormone production, and maintaining normal insulin sensitivity and glucose homeostasis.