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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Nov 27

PMID 34830301

Citations 6

Authors

Olga V Saik

Vadim V Klimontov

Affiliations

Soon will be listed here.

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, , 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.

Citing Articles

Severe hypoglycaemia-induced microglial inflammation damages microvascular endothelial cells, leading to retinal destruction.

Hu Y, Li Z, Li H, Xu Q, Xu C, Lin W Diab Vasc Dis Res. 2024; 21(4):14791641241278506.

PMID: 39187253 PMC: 11348349. DOI: 10.1177/14791641241278506.

Nocturnal Glucose Patterns with and without Hypoglycemia in People with Type 1 Diabetes Managed with Multiple Daily Insulin Injections.

Kladov D, Berikov V, Semenova J, Klimontov V J Pers Med. 2023; 13(10).

PMID: 37888065 PMC: 10608186. DOI: 10.3390/jpm13101454.

Dementia in Diabetes: The Role of Hypoglycemia.

Husain K, Sarhan S, AlKhalifa H, Buhasan A, Moin A, Butler A Int J Mol Sci. 2023; 24(12).

PMID: 37372995 PMC: 10298520. DOI: 10.3390/ijms24129846.

Machine Learning Models for Nocturnal Hypoglycemia Prediction in Hospitalized Patients with Type 1 Diabetes.

Berikov V, Kutnenko O, Semenova J, Klimontov V J Pers Med. 2022; 12(8).

PMID: 36013211 PMC: 9409948. DOI: 10.3390/jpm12081262.

Impairment of Mitochondrial Respiration in Metabolic Diseases: An Overview.

Avram V, Merce A, Hancu I, Batran A, Kennedy G, Rosca M Int J Mol Sci. 2022; 23(16).

PMID: 36012137 PMC: 9408127. DOI: 10.3390/ijms23168852.

References

Li R, Ma J, Wu Y, Nangle M, Zou S, Li Y . Dual Delivery of NGF and bFGF Coacervater Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Schwann Cells Apoptosis. Int J Biol Sci. 2017; 13(5):640-651. PMC: 5441180. DOI: 10.7150/ijbs.18636. View

Yamagishi S, Matsui T . Pleiotropic effects of glucagon-like peptide-1 (GLP-1)-based therapies on vascular complications in diabetes. Curr Pharm Des. 2011; 17(38):4379-85. DOI: 10.2174/138161211798999456. View

Bondeva T, Wolf G . Role of Neuropilin-1 in Diabetic Nephropathy. J Clin Med. 2015; 4(6):1293-311. PMC: 4485001. DOI: 10.3390/jcm4061293. View

Moll L, Schubert M . The Role of Insulin and Insulin-Like Growth Factor-1/FoxO-Mediated Transcription for the Pathogenesis of Obesity-Associated Dementia. Curr Gerontol Geriatr Res. 2012; 2012:384094. PMC: 3359655. DOI: 10.1155/2012/384094. View

Kwok M, Lin S, Schooling C . Re-thinking Alzheimer's disease therapeutic targets using gene-based tests. EBioMedicine. 2018; 37:461-470. PMC: 6446018. DOI: 10.1016/j.ebiom.2018.10.001. View

Ivanisenko V, Saik O, Ivanisenko N, Tiys E, Ivanisenko T, Demenkov P . ANDSystem: an Associative Network Discovery System for automated literature mining in the field of biology. BMC Syst Biol. 2015; 9 Suppl 2:S2. PMC: 4407185. DOI: 10.1186/1752-0509-9-S2-S2. View

Rhee S . Hypoglycemia and Dementia. Endocrinol Metab (Seoul). 2017; 32(2):195-199. PMC: 5503864. DOI: 10.3803/EnM.2017.32.2.195. View

Escribano L, Simon A, Perez-Mediavilla A, Salazar-Colocho P, Del Rio J, Frechilla D . Rosiglitazone reverses memory decline and hippocampal glucocorticoid receptor down-regulation in an Alzheimer's disease mouse model. Biochem Biophys Res Commun. 2008; 379(2):406-10. DOI: 10.1016/j.bbrc.2008.12.071. View

Chabrier P, Auguet M . Nitric oxide synthases: targets for therapeutic strategies in neurological diseases. Cell Mol Life Sci. 1999; 55(8-9):1029-35. PMC: 11146904. DOI: 10.1007/s000180050353. View

10.

Saik O, Demenkov P, Ivanisenko T, Bragina E, Freidin M, Goncharova I . Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks. BMC Med Genomics. 2018; 11(Suppl 1):15. PMC: 6389037. DOI: 10.1186/s12920-018-0331-4. View

11.

Chang J, Lee M, Lin S, Yang L, Sun H, Sze C . Trafficking protein particle complex 6A delta (TRAPPC6AΔ) is an extracellular plaque-forming protein in the brain. Oncotarget. 2015; 6(6):3578-89. PMC: 4414138. DOI: 10.18632/oncotarget.2876. View

12.

Solomon-Zemler R, Basel-Vanagaite L, Steier D, Yakar S, Mel E, Phillip M . A novel heterozygous IGF-1 receptor mutation associated with hypoglycemia. Endocr Connect. 2017; 6(6):395-403. PMC: 5551424. DOI: 10.1530/EC-17-0038. View

13.

Davis S, Duckworth W, Emanuele N, Hayward R, Wiitala W, Thottapurathu L . Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial. Diabetes Care. 2018; 42(1):157-163. PMC: 6463547. DOI: 10.2337/dc18-1144. View

14.

Bragina E, Tiys E, Freidin M, Koneva L, Demenkov P, Ivanisenko V . Insights into pathophysiology of dystropy through the analysis of gene networks: an example of bronchial asthma and tuberculosis. Immunogenetics. 2014; 66(7-8):457-65. DOI: 10.1007/s00251-014-0786-1. View

15.

Carbon S, Ireland A, Mungall C, Shu S, Marshall B, Lewis S . AmiGO: online access to ontology and annotation data. Bioinformatics. 2008; 25(2):288-9. PMC: 2639003. DOI: 10.1093/bioinformatics/btn615. View

16.

Moin A, Kahal H, Al-Qaissi A, Kumar N, Sathyapalan T, Atkin S . Amyloid-related protein changes associated with dementia differ according to severity of hypoglycemia. BMJ Open Diabetes Res Care. 2021; 9(1). PMC: 8098766. DOI: 10.1136/bmjdrc-2021-002211. View

17.

Shi L, Fonseca V, Childs B . Economic burden of diabetes-related hypoglycemia on patients, payors, and employers. J Diabetes Complications. 2021; 35(6):107916. DOI: 10.1016/j.jdiacomp.2021.107916. View

18.

Silva I, Silva J, Ferreira R, Trigo D . Glymphatic system, AQP4, and their implications in Alzheimer's disease. Neurol Res Pract. 2021; 3(1):5. PMC: 7816372. DOI: 10.1186/s42466-021-00102-7. View

19.

Zhou M, Xu R, Kaelber D, Gurney M . Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer's disease in patients with rheumatoid arthritis and psoriasis. PLoS One. 2020; 15(3):e0229819. PMC: 7089534. DOI: 10.1371/journal.pone.0229819. View

20.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View