Expression of the gene encoding glycogen phosphorylase is elevated in diabetic rat skeletal muscle and is regulated by insulin and cyclic AMP.
Expression of the gene encoding glycogen phosphorylase is elevated in diabetic rat skeletal muscle and is regulated by insulin and cyclic AMP.
复制标题
糖尿病大鼠骨骼肌中编码糖原磷酸化酶的基因表达升高，并受到胰岛素和环磷酸腺苷的调节。
DOI：
10.1007/bf00403961
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发表时间：
1996
期刊：
影响因子：
8.2
通讯作者：
Loeken,MR
中科院分区：
文献类型：
--
作者：
Reynet,C;Kahn,CR;Loeken,MR
糖原磷酸化酶调节糖原分解为葡萄糖，但正如之前的研究表明，糖尿病中糖原代谢的控制变得失调。在胰岛素依赖型和非胰岛素依赖型糖尿病患者的骨骼肌活检中，编码几种不同蛋白质的信使 RNA 水平发生了改变。此前尚未研究过糖尿病期间编码骨骼肌糖原磷酸化酶亚型的基因表达可能发生的改变。我们检查了链脲佐菌素诱导的糖尿病和胰岛素治疗对大鼠骨骼肌糖原磷酸化酶 mRNA 的影响；糖尿病大鼠肌肉组织中糖原磷酸化酶 mRNA 水平升高，但胰岛素治疗后糖尿病大鼠肌肉中糖原磷酸化酶 mRNA 水平部分受到抑制。为了区分胰岛素和反调节激素对糖原磷酸化酶 mRNA 水平的影响，我们在培养物中分化了大鼠 L6 成肌细胞。通过 Northern 印迹分析确定，胰岛素刺激了糖原磷酸化酶 mRNA 的积累。此外，在培养物中分化的肌管中，胰岛素和二丁酰cAMP刺激瞬时转染的氯霉素乙酰转移酶报告基因在肌糖原磷酸化酶启动子的控制下表达，这表明胰岛素和反调节激素对糖原磷酸化酶mRNA的影响是在转录水平。这些结果表明，胰岛素和肾上腺素可能参与了肌生成过程中糖原磷酸化酶基因的诱导。此外，肌肉组织中该基因的激活可能是糖尿病不受控制期间糖原储存受损的一个促成因素。
Glycogen phosphorylase regulates the breakdown of glycogen into glucose, but as previous studies have demonstrated, the control of glycogen metabolism becomes deregulated in diabetes mellitus. Messenger RNA levels encoding several different proteins are altered in skeletal muscle biopsies of patients with insulin-dependent and non-insulin-dependent diabetes. The possible alteration of expression of the gene encoding the skeletal muscle isoform of glycogen phosphorylase during diabetes has not previously been investigated. We examined the effect of streptozotocin-induced diabetes and insulin treatment on glycogen phosphorylase mRNA in rat skeletal muscle; glycogen phosphorylase mRNA levels were elevated in diabetic rat muscle tissue, but were partially suppressed in diabetic rat muscle following insulin treatment. To distinguish between the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA levels, we employed differentiating rat L6 myoblasts in culture. Insulin stimulated the accumulation of glycogen phosphorylase mRNA as determined by Northern blot analysis. Moreover, insulin and dibutyryl cAMP stimulated expression of a transiently transfected chloramphenicol acetyl transferase reporter gene under the control of the muscle glycogen phosphorylase promoter in differentiating myotubes in culture, suggesting that the effects of insulin and counter-regulatory hormones on glycogen phosphorylase mRNA are at the level of transcription. These results suggest that insulin and epinephrine may participate in the induction of the glycogen phosphorylase gene during myogenesis; moreover, activation of this gene in muscle tissue may be a contributing factor in impaired glycogen storage during uncontrolled diabetes.