Hernández Cristina, Garcia-Ramírez Marta, García-Rocha Mar, Saez-López Cristina, Valverde Ángela M, Guinovart Joan J, Simó Rafael
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron 119-129, 08035, Barcelona, Spain,
Acta Diabetol. 2014 Aug;51(4):543-52. doi: 10.1007/s00592-013-0549-8. Epub 2014 Jan 24.
Liver and muscle glycogen content is reduced in diabetic patients but there is no information on the effect of diabetes on the glycogen content in the retinal pigment epithelium (RPE). The main aim of the study was to compare the glycogen content in the RPE between diabetic and non-diabetic human donors. Glycogen synthase (GS) and glycogen phosphorylase (GP), the key enzymes of glycogen metabolism, as well as their isoforms, were also assessed. For this purpose, 44 human postmortem eye cups were included (22 from 11 type 2 diabetic and 22 from 11 non-diabetic donors matched by age). Human RPE cells cultured in normoglycemic and hyperglycemic conditions were also analyzed. Glycogen content as well as the mRNA, protein content and enzyme activity of GS and GP were determined. In addition, GS and GP isoforms were characterized. In the RPE from diabetic donors, as well as in RPE cells grown in hyperglycemic conditions, the glycogen content was increased. The increase in glycogen content was associated with an increase in GS without changes in GP levels. In RPE form human donors, the muscle GS isoform but not the liver GS isoform was detected. Regarding GP, the muscle and brain isoform of GP but not the liver GP isoform were detected. We conclude that glycogen storage is increased in the RPE of diabetic patients, and it is associated with an increase in GS activity. Further studies aimed at determining the role of glycogen deposits in the pathogenesis of diabetic retinopathy are warranted.
糖尿病患者肝脏和肌肉中的糖原含量会降低，但关于糖尿病对视网膜色素上皮（RPE）中糖原含量的影响尚无相关信息。本研究的主要目的是比较糖尿病患者和非糖尿病患者供体RPE中的糖原含量。还评估了糖原代谢的关键酶糖原合酶（GS）和糖原磷酸化酶（GP）及其同工型。为此，纳入了44个死后眼球杯（11名2型糖尿病患者的22个和11名年龄匹配的非糖尿病供体的22个）。还分析了在正常血糖和高血糖条件下培养的人RPE细胞。测定了糖原含量以及GS和GP的mRNA、蛋白质含量和酶活性。此外，还对GS和GP同工型进行了表征。在糖尿病供体的RPE以及在高血糖条件下生长的RPE细胞中，糖原含量增加。糖原含量的增加与GS的增加相关，而GP水平没有变化。在人类供体的RPE中，检测到肌肉GS同工型但未检测到肝脏GS同工型。关于GP，检测到GP的肌肉和脑同工型但未检测到肝脏GP同工型。我们得出结论，糖尿病患者RPE中的糖原储存增加，并且这与GS活性的增加相关。有必要进行进一步的研究以确定糖原沉积在糖尿病视网膜病变发病机制中的作用。
