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Comparison of anti-apoptotic signalling by the insulin receptor and IGF-I receptor in preadipocytes and adipocytes

机译:胰岛素受体和IGF-I受体在前脂肪细胞和脂肪细胞中抗凋亡信号的比较

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We compared the effectiveness of insulin receptor (IR) and type I insulin-like growth factor (IGF) receptor (IGFR) cytoplasmic domains in mediating anti-apoptotic effects in 3T3-L1 preadipocytes and adipocytes. We used TrkC/IR and TrkC/IGFR chimeras, stably expressed in these cells and stimulated with neurotrophin-3 (NT-3), so as to avoid interference from endogenous receptors. After 24-h serum deprivation, 10% of preadipocytes and 2% of adipocytes appeared apoptotic as determined by fluorescence-activated cell sorter (FACS) analysis of cells stained with propidium iodide (PI) and Annexin V. When NT-3 was added, the two chimeras inhibited apoptosis to the same extent by 80% in preadipocytes and 50% in adipocytes. Mutation of juxtamembrane tyrosines OR Y960F, IGFR Y950F) abrogated these anti-apoptotic effects. Qualitatively similar results were obtained by determination of viable rather than apoptotic cells. We conclude that LR and IGFR have equal potential to inhibit apoptosis in cell backgrounds, which are normally responsive to either IGF-I or insulin. (C) 2001 Elsevier Science Inc. All rights reserved. [References: 53]
机译:我们比较了胰岛素受体(IR)和I型胰岛素样生长因子(IGF)受体(IGFR)胞质域在介导3T3-L1前脂肪细胞和脂肪细胞中抗凋亡作用中的有效性。我们使用了在这些细胞中稳定表达并用Neurotrophin-3(NT-3)刺激的TrkC / IR和TrkC / IGFR嵌合体,以避免内源性受体的干扰。血清剥夺24小时后,通过对碘化丙锭(PI)和膜联蛋白V染色的细胞进行荧光激活细胞分选(FACS)分析,可以确定10%的前脂肪细胞和2%的脂肪细胞出现凋亡。添加NT-3时,两种嵌合体在前脂肪细胞中抑制凋亡的程度相同,分别为80%和50%。近膜酪氨酸或Y960F,IGFR Y950F的突变消除了这些抗凋亡作用。通过测定存活细胞而不是凋亡细胞获得了定性相似的结果。我们得出的结论是,LR和IGFR具有相同的潜力来抑制通常对IGF-1或胰岛素有反应的细胞背景中的凋亡。 (C)2001 Elsevier Science Inc.保留所有权利。 [参考:53]

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