Glucolipotoxicity age-dependently impairs beta cell function in rats despite a marked increase in beta cell mass.
Glucolipotoxicity age-dependently impairs beta cell function in rats despite a marked increase in beta cell mass.
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DOI：
10.1007/s00125-010-1850-5
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发表时间：
2010-11
期刊：
影响因子：
8.2
通讯作者：
Poitout, V.
中科院分区：
文献类型：
--
作者：
Fontes, G.;Zarrouki, B.;Hagman, D. K.;Latour, M. G.;Semache, M.;Roskens, V.;Moore, P. C.;Prentki, M.;Rhodes, C. J.;Jetton, T. L.;Poitout, V.
关键词：
据推测，胰腺β细胞长时间暴露于过量的葡萄糖和脂肪酸（称为糖脂毒性）会导致2型糖尿病患者的葡萄糖稳态受损。然而，在体内糖脂毒性条件下，β细胞功能缺陷与β细胞质量减少的相对贡献仍然是一个争论的话题。因此，我们试图确定大鼠中的糖脂毒性是否是由于β细胞功能受损和/或β细胞质量减少所致，以及老年动物是否更容易受到糖脂毒性状况的影响。 Wistar 大鼠（2 个月和 6 个月大）接受 72 小时输注葡萄糖 + 静脉脂肪乳或盐水对照。通过高血糖钳评估体内胰岛素分泌和敏感性。在分离的胰岛中测量离体胰岛素分泌、胰岛素生物合成和基因表达。通过免疫组织化学检查β细胞质量和增殖。 2月龄Wistar大鼠72小时输注葡萄糖+静脉脂肪乳不影响胰岛素敏感性、胰岛素分泌或β细胞质量。相比之下，在 6 个月大的大鼠中，尽管 β 细胞质量和增殖有所增加，但它会导致胰岛素抵抗并减少体内胰岛素分泌。这与：（1）葡萄糖刺激的第二相胰岛素分泌和胰岛素原生物合成减少； (2)降低胰岛素含量； (3) 分离胰岛中β细胞基因的表达减少。在该体内模型中，糖脂毒性的特征是，尽管β细胞质量显着增加，但葡萄糖调节的β细胞功能出现年龄依赖性损伤。
Prolonged exposure of pancreatic beta cells to excessive levels of glucose and fatty acids, referred to as glucolipotoxicity, is postulated to contribute to impaired glucose homeostasis in patients with type 2 diabetes. However, the relative contribution of defective beta cell function vs diminished beta cell mass under glucolipotoxic conditions in vivo remains a subject of debate. We therefore sought to determine whether glucolipotoxicity in rats is due to impaired beta cell function and/or reduced beta cell mass, and whether older animals are more susceptible to glucolipotoxic condition. Wistar rats (2 and 6 months old) received a 72 h infusion of glucose + intravenous fat emulsion or saline control. In vivo insulin secretion and sensitivity were assessed by hyperglycaemic clamps. Ex vivo insulin secretion, insulin biosynthesis and gene expression were measured in isolated islets. Beta cell mass and proliferation were examined by immunohistochemistry. A 72 h infusion of glucose + intravenous fat emulsion in 2-month-old Wistar rats did not affect insulin sensitivity, insulin secretion or beta cell mass. In 6-month-old rats by contrast it led to insulin resistance and reduced insulin secretion in vivo, despite an increase in beta cell mass and proliferation. This was associated with: (1) diminished glucose-stimulated second-phase insulin secretion and proinsulin biosynthesis; (2) lower insulin content; and (3) reduced expression of beta cell genes in isolated islets. In this in vivo model, glucolipotoxicity is characterised by an age-dependent impairment of glucose-regulated beta cell function despite a marked increase in beta cell mass.
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影响因子：
7.7
作者：
Hagman, Derek K.;Latour, Martin G.;Poitout, Vincent
通讯作者：
Poitout, Vincent
DOI：
10.1152/ajpendo.00255.2006
发表时间：
2007-02-01
影响因子：
5.1
作者：
Goh, Tracy T.;Mason, Timothy M.;Giacca, Adria
通讯作者：
Giacca, Adria
影响因子：
7.7
作者：
Lupi, R;Dotta, F;Marchetti, P
通讯作者：
Marchetti, P
影响因子：
7.7
作者：
Briaud, I;Harmon, JS;Poitout, V
通讯作者：
Poitout, V
影响因子：
7.7
作者：
BODEN, G;CHEN, XH;BARTON, M
通讯作者：
BARTON, M