Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Leprdb) and obese (DBA-Lepob) mice
Differential beta cell responses to hyperglycaemia and insulin resistance in two novel congenic strains of diabetes (FVB-Leprdb) and obese (DBA-Lepob) mice
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DOI：
10.1007/s00125-002-0880-z
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发表时间：
2002-07-01
期刊：
影响因子：
8.2
通讯作者：
Fisher, P
中科院分区：
文献类型：
--
作者：
Chua, S;Liu, SM;Fisher, P
目标。我们的目标是确定决定胰岛素抵抗和高血糖反应的遗传变异。本报告记录了通过将Lepr（db）突变转移到FVB/NJ品系和将Lep（ob）突变转移到DBA/2 J品系而产生的两个新的同类系小鼠的糖尿病综合征。通过测量血液代谢物和激素沿着葡萄糖和胰岛素注射的挑战来表征小鼠。对内分泌胰腺和肾脏进行组织学检查。FVB-db同类系的肥胖小鼠表现出长期高血糖，这主要是由于严重的胰岛素抵抗。尽管胰岛素分泌增加和胰腺β细胞大量增加，但进食状态下的高血糖症仍持续存在。肥胖FVB-db小鼠显示肾小球系膜基质扩张的证据，这是糖尿病肾病的标志。DBA-ob品系的瘦素缺陷小鼠具有可变的肥胖-糖尿病。在具有高胰岛素（>10 ng/ml）的小鼠中，DBA-ob/ob小鼠保持其增加的肥胖并且具有β细胞数量的大幅增加。在低胰岛素的小鼠中（
Aims. Our goal was to identify genetic variants that determine the response to insulin resistance and hyperglycaemia. This report documents the diabetes syndrome of two new congenic strains of mice generated by the transfer of the Lepr(db) mutation to the FVB/NJ strain and the Lep(ob) mutation to the DBA/2J strain.Methods. Mice were characterised by measures of blood metabolites and hormones along with challenges with glucose and insulin injections. Histological examinations of the endocrine pancreas and the kidneys were also carried out.Results. Obese mice of the FVB-db congenic strain show long-term hyperglycaemia that is primarily due to severe insulin resistance. The hyperglycaemia in the fed state persists despite escalating secretion of insulin and massive increase of pancreatic beta cells. Obese FVB-db mice show evidence of mesangial matrix expansion, a hallmark of diabetic nephropathy. Leptin-deficient mice of the DBA-ob strain have variable obesity-diabetes. In mice with high insulin (>10 ng/ml), DBA-ob/ob mice maintain their increased adiposity and have a large increase in beta-cell number. In mice with low insulin (