EFFECTS OF STREPTOZOTOCIN TREATMENT IN GROWTH-HORMONE (GH) AND GH ANTAGONIST TRANSGENIC MICE
EFFECTS OF STREPTOZOTOCIN TREATMENT IN GROWTH-HORMONE (GH) AND GH ANTAGONIST TRANSGENIC MICE
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DOI：
10.1210/en.136.2.660
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发表时间：
1995-02-01
期刊：
影响因子：
4.8
通讯作者：
KOPCHICK, JJ
中科院分区：
文献类型：
--
作者：
CHEN, NY;CHEN, WY;KOPCHICK, JJ
为了探讨生长激素在糖尿病终末器官损害中的作用，用链脲佐菌素(STZ)诱导牛生长激素(BGH)或BGH拮抗剂转基因小鼠及其非转基因(NTG)小鼠的实验性糖尿病。对这些动物的生长、血糖、血清胰岛素样生长因子-I水平、肝脏生长激素受体(GHR)结合和肾脏组织学进行评估。在多次低剂量注射STZ后，90%的小鼠出现高血糖。糖尿病动物，特别是那些表达GH和GH拮抗剂转基因的动物，与它们的非糖尿病小鼠相比，表现出身体生长迟缓和胰岛素样生长因子-I水平降低。肾脏组织学显示糖尿病和非糖尿病BGH转基因小鼠有严重的肾小球硬化。糖尿病NTG小鼠表现为中度肾脏损害。糖尿病BGH拮抗剂转基因小鼠的肾小球正常，与非糖尿病NTG小鼠的肾小球无法区分。GHR结合分析显示，与非糖尿病对照组相比，糖尿病NTG小鼠和转基因侏儒小鼠的肝脏GHR结合位点显著减少。相反，BGH转基因小鼠的肝脏GHR结合能力显著高于它们的NTG小鼠，并在糖尿病期间保持较高水平。结论是，表达生长激素拮抗剂的转基因小鼠可以预防糖尿病和/或生长激素诱导的肾病。
To investigate GH's role in diabetic end organ damage, experimental diabetes was induced with streptozotocin (STZ) in bovine GH (bGH) or bGH antagonist transgenic mice and in their nontransgenic (NTG) litter mates. Body growth, blood glucose, serum insulin-like growth factor-I levels, liver GH receptor (GHR) binding, and kidney histology of these animals were evaluated. After administration of multiple low doses of STZ, 90% of the mice developed hyperglycemia. The diabetic animals, especially those expressing GH and GH antagonist transgenes, demonstrated retarded body growth and reduced insulin-like growth factor-I levels when compared with their nondiabetic litter mates. Kidney histology revealed severe glomerulosclerosis in diabetic and nondiabetic bGH transgenic mice. Diabetic NTG mice exhibited moderate kidney lesions. Diabetic bGH antagonist transgenic mice possessed normal glomeruli indistinguishable from those seen in nondiabetic NTG mice. GHR-binding assays revealed that liver GHR-binding sites were significantly reduced in diabetic NTG mice and transgenic dwarf mice when compared with their nondiabetic controls. Conversely, liver GHR-binding ability was significantly increased in bGH transgenic mice as compared with their NTG littermates and remained high during diabetes. It is concluded that transgenic mice that express a GH antagonist are protected from diabetes and or GH-induced nephropathy.