Pancreatic -Cells in Obesity
Pancreatic -Cells in Obesity
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肥胖中的胰腺细胞
DOI：
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发表时间：
1995
影响因子：
4.8
通讯作者：
R. Unger
中科院分区：
文献类型：
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作者：
J. L. Milburn;H. Hirose;Y. Lee;Y. Nagasawa;A. Ogawa;M. Ohneda;H. Beltrandelrio;C. Newgard;John H. Johnson;R. Unger
为了阐明肥胖基础高胰岛素血症的机制，我们用亚刺激浓度的葡萄糖灌注肥胖Zucker和瘦Wistar大鼠的胰腺。在4.2和5.6 mM葡萄糖下的胰岛素分泌是对照的10倍，而β细胞体积分数仅增加4倍，每个胰岛的DNA增加3.5倍。因此，我们比较了1.4、2.8和5.6 mM葡萄糖的使用。在1.4和2.8 mM下，Zucker胰岛的使用率高8-11.4倍，在5.6 mM下高4倍;在2.8和5.6 mM葡萄糖下的葡萄糖氧化是瘦对照的12倍。为了确定肥胖的高游离脂肪酸（FFA）水平是否诱导这些异常，将正常Wistar胰岛与0、1或2 mM长链FFA培养7天。与无FFA培养的胰岛相比，用1.4、3或5.6 mM葡萄糖灌注的FFA培养的胰岛（2 mM）的胰岛素分泌增加超过2倍，溴脱氧尿苷掺入增加3倍，2.8和5.6 mM葡萄糖的葡萄糖使用增加约2倍（1 mM FFA）和3倍（2 mM FFA）。我们的结论是，肥胖Zucker肥胖大鼠胰岛的胰岛素分泌过多与增强的低钾葡萄糖代谢和β细胞增生有关，并且可能是由其引起的，这些异常可以通过增加FFA在正常胰岛中诱导。
To elucidate the mechanism of the basal hyperinsulinemia of obesity, we perfused pancreata from obese Zucker and lean Wistar rats with substimulatory concentrations of glucose. Insulin secretion at 4.2 and 5.6 mM glucose was 10 times that of controls, whereas β-cell volume fraction was increased only 4-fold and DNA per islet 3.5-fold. We therefore compared glucose usage at 1.4, 2.8, and 5.6 mM. Usage was 8-11.4 times greater in Zucker islets at 1.4 and 2.8 mM and 4 times greater at 5.6 mM; glucose oxidation at 2.8 and 5.6 mM glucose was >12 times lean controls. To determine if the high free fatty acid (FFA) levels of obesity induce these abnormalities, normal Wistar islets were cultured with 0, 1, or 2 mM long chain FFA for 7 days. Compared to islets cultured without FFA insulin secretion by FFA-cultured islets (2 mM) perifused with 1.4, 3, or 5.6 mM glucose was increased more than 2-fold, bromodeoxyuridine incorporation was increased 3-fold, and glucose usage at 2.8 and 5.6 mM glucose was increased approximately 2-fold (1 mM FFA) and 3-fold (2 mM FFA). We conclude that hypersecretion of insulin by islets of obese Zucker fatty rats is associated with, and probably caused by, enhanced low K glucose metabolism and β-cell hyperplasia, abnormalities that can be induced in normal islets by increased FFA.