Laboratory of Endocrinology, Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL-Branch of ICG SB RAS), 630060 Novosibirsk, Russia.
Laboratory of Computer Proteomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences (ICG SB RAS), 630090 Novosibirsk, Russia.
Int J Mol Sci. 2021 Nov 17;22(22):12419. doi: 10.3390/ijms222212419.
Hypoglycemia has been recognized as a risk factor for diabetic vascular complications and cognitive decline, but the molecular mechanisms of the effect of hypoglycemia on target organs are not fully understood. In this work, gene networks of hypoglycemia and cardiovascular disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, cognitive decline, and Alzheimer's disease were reconstructed using ANDSystem, a text-mining-based tool. The gene network of hypoglycemia included 141 genes and 2467 interactions. Enrichment analysis of Gene Ontology (GO) biological processes showed that the regulation of insulin secretion, glucose homeostasis, apoptosis, nitric oxide biosynthesis, and cell signaling are significantly enriched for hypoglycemia. Among the network hubs, , and had the highest betweenness centrality, while , and demonstrated the highest cross-talk specificity. Hypoglycemia-related genes were overrepresented in the gene networks of diabetic complications and comorbidity; moreover, 14 genes were mutual for all studied disorders. Eleven GO biological processes (glucose homeostasis, nitric oxide biosynthesis, smooth muscle cell proliferation, ERK1 and ERK2 cascade, etc.) were overrepresented in all reconstructed networks. The obtained results expand our understanding of the molecular mechanisms underlying the deteriorating effects of hypoglycemia in diabetes-associated vascular disease and cognitive dysfunction.
低血糖已被认为是糖尿病血管并发症和认知能力下降的危险因素，但低血糖对靶器官影响的分子机制尚不完全清楚。本研究采用基于文本挖掘的工具 ANDSystem，构建了低血糖与心血管疾病、糖尿病视网膜病变、糖尿病肾病、糖尿病神经病变、认知能力下降和阿尔茨海默病的基因网络。低血糖的基因网络包含 141 个基因和 2467 个相互作用。GO 生物过程富集分析显示，胰岛素分泌调节、葡萄糖稳态、细胞凋亡、一氧化氮生物合成和细胞信号转导对低血糖有显著富集。在网络枢纽中， 、 和 具有最高的介数中心性，而 、 和 表现出最高的交叉特异性。低血糖相关基因在糖尿病并发症和合并症的基因网络中过度表达；此外，所有研究的疾病中有 14 个基因是相互的。在所有重建的网络中，有 11 个 GO 生物过程（葡萄糖稳态、一氧化氮生物合成、平滑肌细胞增殖、ERK1 和 ERK2 级联等）过表达。研究结果扩展了我们对糖尿病相关血管疾病和认知功能障碍中低血糖恶化作用的分子机制的理解。
