Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks

• Published in: International journal of molecular sciences Vol. 22; no. 22; p. 12419
• Main Authors: Saik, Olga V, Klimontov, Vadim V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.11.2021; MDPI
• Subjects: Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Apoptosis; Artificial intelligence; Bioinformatics; Biological activity; Biosynthesis; Brain research; cardiovascular disease; Cardiovascular diseases; Cell proliferation; cognitive dysfunction; Cognitive Dysfunction - epidemiology; Cognitive Dysfunction - genetics; Comorbidity; Computational Biology - methods; Crosstalk; Data Mining - methods; Databases, Genetic; Dementia; Diabetes; Diabetes mellitus; Diabetic Angiopathies - epidemiology; Diabetic Angiopathies - genetics; Diabetic nephropathy; Diabetic neuropathy; Diabetic retinopathy; Gene expression; Gene Regulatory Networks; Genes; Glucagon; Glucose; Growth hormones; Homeostasis; Humans; Hypoglycemia; Hypoglycemia - epidemiology; Hypoglycemia - genetics; Insulin; Insulin secretion; Insulin-like growth factor-binding protein 6; Interleukin 1; Interleukin 6; Metabolism; MicroRNAs; Molecular modelling; Muscles; Nephropathy; Network hubs; Neuropeptides; Nitric oxide; Organs; Polypeptides; Protein Interaction Maps - genetics; Proteins; Retinopathy; Risk analysis; Risk Factors; Signal Transduction - genetics; Smooth muscle; Transcription factors; Vascular diseases; Russia; cardiovascular disease; Alzheimer’s disease; gene networks; diabetic neuropathy; ANDsystem; hypoglycemia; diabetic retinopathy; cognitive dysfunction; diabetes; diabetic nephropathy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.