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

Saik, Olga V.; Klimontov, Vadim V.

doi:10.3390/ijms222212419

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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

Olga V. Saik

^1,2 and

Vadim V. Klimontov

^1,*

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

Author to whom correspondence should be addressed.

Academic Editor: Ramzi Ajjan

Int. J. Mol. Sci. 2021, 22(22), 12419; https://doi.org/10.3390/ijms222212419

Received: 20 October 2021 / Revised: 14 November 2021 / Accepted: 16 November 2021 / Published: 17 November 2021

(This article belongs to the Special Issue Molecular Pathways for Vascular Risk in Diabetes)

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Abstract

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, INS, IL6, LEP, TNF, IL1B, EGFR, and FOS had the highest betweenness centrality, while GPR142, MBOAT4, SLC5A4, IGFBP6, PPY, G6PC1, SLC2A2, GYS2, GCGR, and AQP7 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. View Full-Text

Keywords: hypoglycemia; diabetes; cardiovascular disease; diabetic retinopathy; diabetic nephropathy; cognitive dysfunction; Alzheimer’s disease; diabetic neuropathy; gene networks; ANDsystem

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Saik, O.V.; Klimontov, V.V. Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks. Int. J. Mol. Sci. 2021, 22, 12419. https://doi.org/10.3390/ijms222212419

AMA Style

Saik OV, Klimontov VV. Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks. International Journal of Molecular Sciences. 2021; 22(22):12419. https://doi.org/10.3390/ijms222212419

Chicago/Turabian Style

Saik, Olga V., and Vadim V. Klimontov. 2021. "Hypoglycemia, Vascular Disease and Cognitive Dysfunction in Diabetes: Insights from Text Mining-Based Reconstruction and Bioinformatics Analysis of the Gene Networks" International Journal of Molecular Sciences 22, no. 22: 12419. https://doi.org/10.3390/ijms222212419

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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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