The effect of global SSTR5 gene ablation on the endocrine pancreas and glucose regulation in aging mice.
The effect of global SSTR5 gene ablation on the endocrine pancreas and glucose regulation in aging mice.
复制标题
整体 SSTR5 基因消融对衰老小鼠内分泌胰腺和葡萄糖调节的影响。
DOI：
10.1016/j.jss.2005.05.024
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Brunicardi,FC
中科院分区：
文献类型：
--
作者：
Wang,XP;Norman,M;Yang,J;Liu,SH;Magnusson,J;DeMayo,FJ;Brunicardi,FC
[目的]由于SSTR5是小鼠胰腺胰岛素分泌的主要调节因子，本研究旨在探讨SSTR5基因整体切除对衰老小鼠胰腺内分泌、胰岛素分泌和糖耐量的影响。方法建立全球SSTR5−/−小鼠，采用Southern印迹和RT-PCR法进行基因分型。分别于3月龄和12月龄(每组8只)采用腹腔葡萄糖耐量试验(IPGTT1.2~2.0 mg/kg)检测SSTR5、−/−和WT小鼠的糖耐量和体内胰岛素分泌。分别在3个月和12个月时采用小鼠胰腺离体灌流法研究基础胰岛素和葡萄糖刺激下的胰岛素分泌。取胰腺，用免疫组织化学方法结合H&E染色检测胰岛素、胰升糖素、生长抑素和生长抑素受体的水平。结果SSTR5−/−小鼠的基因分型证实SSTR5基因缺失。IPGTT显示，3个月大的SSTR5−/−小鼠虽然体内和体外的胰岛素分泌相似，但胰岛扩大，但仍存在糖耐量异常。在12个月龄时，SSTR5−/−小鼠在体内和体外都有基础低血糖和糖耐量异常改善，并伴有高胰岛素血症和扩大的胰岛。SSTR5−/−小鼠在3个月和12个月龄时胰岛素清除量增加。结论SSTR5和SSTR1在小鼠胰岛素分泌和血糖调节中均起关键作用，其调节作用与年龄有关。结论SSTR5和SSTR1在3月龄小鼠胰岛素分泌和血糖调节中起重要作用，但在12月龄时−/−小鼠胰岛生长抑素几乎不表达。
INTRODUCTIONThe purpose of this study was to examine the effect of global gene ablation of SSTR5 on the endocrine pancreas, insulin secretion, and glucose tolerance in aging mice, as SSTR5 is a primary regulator of insulin secretion in the mouse pancreas.METHODSGlobal SSTR5−/−mice were generated and genotypes were verified using Southern blot and RT-PCR. Glucose tolerance and in vivo insulin secretion in SSTR5−/−and WT mice were examined using intraperitoneal glucose tolerance test (IPGTT;1.2–2.0 mg/kg) at 3 and 12 months of age (n = 8 per group). Basal and glucose-stimulated insulin secretion in vitro was studied using the isolated perfused mouse pancreas model at 3 and 12 months. Pancreata were removed and levels of insulin, glucagon, somatostatin, and SSTR1 were studied using immunohistochemical analysis along with H&E staining of the pancreata.RESULTSGenotyping verified the absence of SSTR5 in SSTR5−/−mice. IPGTT demonstrated that 3-month-old SSTR5−/−mice were glucose intolerant despite similar insulin secretion both in vivo and in vitro and enlarged islets. At 12 months of age, SSTR5−/−mice had basal hypoglycemia and improved glucose intolerance associated with hyperinsulinemia in vivo and in vitro and enlarged islets. SSTR5−/−mice had increased insulin clearance at 3 and 12 months of age. SSTR1 expression was significantly increased in islets at 3 months of age, but was nearly absent in islets at 12 months of age, as was somatostatin staining in SSTR5−/−mice.CONCLUSIONSThese results suggest that both SSTR5 and SSTR1 play a pivotal role in insulin secretion and glucose regulation in mice and that their regulatory effects are age-related.
影响因子：
37.8
作者：
DEAMBROGGI, L;BERTONI, T;SCHWARTZ, PJ
通讯作者：
SCHWARTZ, PJ