Effects of insulin and transgenic overexpression of UDP-glucose pyrophosphorylase on UDP-glucose and glycogen accumulation in skeletal muscle fibers.

Effects of insulin and transgenic overexpression of UDP-glucose pyrophosphorylase on UDP-glucose and glycogen accumulation in skeletal muscle fibers.
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胰岛素和 UDP-葡萄糖焦磷酸化酶转基因过表达对骨骼肌纤维中 UDP-葡萄糖和糖原积累的影响。

DOI:
10.1074/jbc.m413614200
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发表时间:
2005
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
LawrenceJr,JohnC
LawrenceJr,JohnC
中科院分区:
--
文献类型:
--
作者:
Reynolds4th,ThomasH;Pak,Yunbae;Harris,ThurlE;Manchester,Jill;Barrett,EugeneJ;LawrenceJr,JohnC

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使用微量分析方法测量特定纤维类型的骨骼肌纤维中的 UDP-葡萄糖 (UDP-Glc) 和糖原水平。给大鼠输注胰岛素会增加 I 型和 II 型纤维中的糖原。胰岛素对 I 型纤维中的 UDP-Glc 没有影响,但使 IIA/D 型和 IIB 型纤维中的 UDP-Glc 降低 35-40%。 UDP-Glc 的减少表明 UDP-Glc 焦磷酸化酶 (PPL) 活性可能限制响应胰岛素的糖原合成。为了探索这种可能性,我们培育了在骨骼肌中过度表达 UDP-Glc PPL 转基因的小鼠。转基因使骨骼肌中 UDP-Glc PPL 活性和 UDP-Glc 水平增加约 3 倍。然而,UDP-Glc PPL 的过度表达对体内骨骼肌糖原水平或葡萄糖耐量没有影响。转基因对体外培养的肌肉中14 C-葡萄糖掺入糖原的对照或胰岛素刺激速率也没有影响。结果表明 UDP-Glc PPL 活性并不限制糖原合成。
UDP-glucose (UDP-Glc) and glycogen levels in skeletal muscle fibers of defined fiber type were measured using microanalytical methods. Infusing rats with insulin increased glycogen in both Type I and Type II fibers. Insulin was without effect on UDP-Glc in Type I fibers but decreased UDP-Glc by 35–40% in Type IIA/D and Type IIB fibers. The reduction in UDP-Glc suggested that UDP-Glc pyrophosphorylase (PPL) activity might limit glycogen synthesis in response to insulin. To explore this possibility, we generated mice overexpressing a UDP-Glc PPL transgene in skeletal muscle. The transgene increased both UDP-Glc PPL activity and levels of UDP-Glc in skeletal muscles by ∼3-fold. However, overexpression of UDP-Glc PPL was without effect on either the levels of skeletal muscle glycogen or glucose tolerancein vivo. The transgene was also without effect on either control or insulin-stimulated rates of14C-glucose incorporation into glycogen in muscles incubatedin vitro. The results indicate that UDP-Glc PPL activity is not limiting for glycogen synthesis.
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