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

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 retinopa...

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Autores principales:	Olga V. Saik, Vadim V. Klimontov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hypoglycemia diabetes cardiovascular disease diabetic retinopathy diabetic nephropathy cognitive dysfunction Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/64603f7b59d5443194d2959e45f540e5
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spelling	oai:doaj.org-article:64603f7b59d5443194d2959e45f540e52021-11-25T17:56:29ZHypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks10.3390/ijms2222124191422-00671661-6596https://doaj.org/article/64603f7b59d5443194d2959e45f540e52021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12419https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Hypoglycemia 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, <i>INS, IL6, LEP, TNF, IL1B, EGFR</i>, and <i>FOS</i> had the highest betweenness centrality, while <i>GPR142, MBOAT4, SLC5A4, IGFBP6, PPY, G6PC1, SLC2A2, GYS2, GCGR</i>, and <i>AQP7</i> 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.Olga V. SaikVadim V. KlimontovMDPI AGarticlehypoglycemiadiabetescardiovascular diseasediabetic retinopathydiabetic nephropathycognitive dysfunctionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12419, p 12419 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoglycemia diabetes cardiovascular disease diabetic retinopathy diabetic nephropathy cognitive dysfunction Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	hypoglycemia diabetes cardiovascular disease diabetic retinopathy diabetic nephropathy cognitive dysfunction Biology (General) QH301-705.5 Chemistry QD1-999 Olga V. Saik Vadim V. Klimontov Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
description	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, <i>INS, IL6, LEP, TNF, IL1B, EGFR</i>, and <i>FOS</i> had the highest betweenness centrality, while <i>GPR142, MBOAT4, SLC5A4, IGFBP6, PPY, G6PC1, SLC2A2, GYS2, GCGR</i>, and <i>AQP7</i> 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.
format	article
author	Olga V. Saik Vadim V. Klimontov
author_facet	Olga V. Saik Vadim V. Klimontov
author_sort	Olga V. Saik
title	Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
title_short	Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
title_full	Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
title_fullStr	Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
title_full_unstemmed	Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks
title_sort	hypoglycemia, vascular disease and cognitive dysfunction in diabetes: insights from text mining-based reconstruction and bioinformatics analysis of the gene networks
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/64603f7b59d5443194d2959e45f540e5
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Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks

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