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MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes

Hypoglycemia, as a complication of type 2 diabetes (T2D), causes increased morbidity and mortality but the physiological response underlying hypoglycemia has not been fully elucidated. Small noncoding microRNA (miRNA) have multiple downstream biological effects. This pilot exploratory study was unde...

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Autores principales: Ramanjaneya, Manjunath, Bettahi, Ilham, Pawar, Krunal, Halabi, Najeeb M., Moin, Abu Saleh Md, Sathyapalan, Thozhukat, Abou-Samra, Abdul Badi, Atkin, Stephen L., Butler, Alexandra E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736413/
https://www.ncbi.nlm.nih.gov/pubmed/36499023
http://dx.doi.org/10.3390/ijms232314696
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author Ramanjaneya, Manjunath
Bettahi, Ilham
Pawar, Krunal
Halabi, Najeeb M.
Moin, Abu Saleh Md
Sathyapalan, Thozhukat
Abou-Samra, Abdul Badi
Atkin, Stephen L.
Butler, Alexandra E.
author_facet Ramanjaneya, Manjunath
Bettahi, Ilham
Pawar, Krunal
Halabi, Najeeb M.
Moin, Abu Saleh Md
Sathyapalan, Thozhukat
Abou-Samra, Abdul Badi
Atkin, Stephen L.
Butler, Alexandra E.
author_sort Ramanjaneya, Manjunath
collection PubMed
description Hypoglycemia, as a complication of type 2 diabetes (T2D), causes increased morbidity and mortality but the physiological response underlying hypoglycemia has not been fully elucidated. Small noncoding microRNA (miRNA) have multiple downstream biological effects. This pilot exploratory study was undertaken to determine if induced miRNA changes would persist and contribute to effects seen 24 h post-hypoglycemia. A parallel, prospective study design was employed, involving T2D (n = 23) and control (n = 23) subjects. The subjects underwent insulin-induced hypoglycemia (2 mmol/L; 36 mg/dL); blood samples were drawn at baseline, upon the induction of hypoglycemia, and 4 h and 24 h post-hypoglycemia, with a quantitative polymerase chain reaction analysis of miRNA undertaken. The baseline miRNAs did not differ. In the controls, 15 miRNAs were downregulated and one was upregulated (FDR < 0.05) from the induction of hypoglycemia to 4 h later while, in T2D, only four miRNAs were altered (downregulated), and these were common to both cohorts (miR-191-5p; miR-143-3p; let-7b-5p; let-7g-5p), correlated with elevated glucagon levels, and all were associated with energy balance. From the induction of hypoglycemia to 24 h, 14 miRNAs were downregulated and 5 were upregulated (FDR < 0.05) in the controls; 7 miRNAs were downregulated and 7 upregulated (FDR < 0.05) in T2D; a total of 6 miRNAs were common between cohorts, 5 were downregulated (miR-93-5p, let-7b-5p, miR-191-5p, miR-185-5p, and miR-652-3p), and 1 was upregulated (miR-369-3p). An ingenuity pathway analysis indicated that many of the altered miRNAs were associated with metabolic and coagulation pathways; however, of the inflammatory proteins expressed, only miR-143-3p at 24 h correlated positively with tumor necrosis factor-α (TNFa; p < 0.05 and r = 0.46) and negatively with toll-like receptor-4 (TLR4; p < 0.05 and r = 0.43). The MiRNA levels altered by hypoglycemia reflected changes in counter-regulatory glucagon and differed between cohorts, and their expression at 24 h suggests miRNAs may potentiate and prolong the physiological response. Trial registration: ClinicalTrials.gov NCT03102801.
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spelling pubmed-97364132022-12-11 MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes Ramanjaneya, Manjunath Bettahi, Ilham Pawar, Krunal Halabi, Najeeb M. Moin, Abu Saleh Md Sathyapalan, Thozhukat Abou-Samra, Abdul Badi Atkin, Stephen L. Butler, Alexandra E. Int J Mol Sci Article Hypoglycemia, as a complication of type 2 diabetes (T2D), causes increased morbidity and mortality but the physiological response underlying hypoglycemia has not been fully elucidated. Small noncoding microRNA (miRNA) have multiple downstream biological effects. This pilot exploratory study was undertaken to determine if induced miRNA changes would persist and contribute to effects seen 24 h post-hypoglycemia. A parallel, prospective study design was employed, involving T2D (n = 23) and control (n = 23) subjects. The subjects underwent insulin-induced hypoglycemia (2 mmol/L; 36 mg/dL); blood samples were drawn at baseline, upon the induction of hypoglycemia, and 4 h and 24 h post-hypoglycemia, with a quantitative polymerase chain reaction analysis of miRNA undertaken. The baseline miRNAs did not differ. In the controls, 15 miRNAs were downregulated and one was upregulated (FDR < 0.05) from the induction of hypoglycemia to 4 h later while, in T2D, only four miRNAs were altered (downregulated), and these were common to both cohorts (miR-191-5p; miR-143-3p; let-7b-5p; let-7g-5p), correlated with elevated glucagon levels, and all were associated with energy balance. From the induction of hypoglycemia to 24 h, 14 miRNAs were downregulated and 5 were upregulated (FDR < 0.05) in the controls; 7 miRNAs were downregulated and 7 upregulated (FDR < 0.05) in T2D; a total of 6 miRNAs were common between cohorts, 5 were downregulated (miR-93-5p, let-7b-5p, miR-191-5p, miR-185-5p, and miR-652-3p), and 1 was upregulated (miR-369-3p). An ingenuity pathway analysis indicated that many of the altered miRNAs were associated with metabolic and coagulation pathways; however, of the inflammatory proteins expressed, only miR-143-3p at 24 h correlated positively with tumor necrosis factor-α (TNFa; p < 0.05 and r = 0.46) and negatively with toll-like receptor-4 (TLR4; p < 0.05 and r = 0.43). The MiRNA levels altered by hypoglycemia reflected changes in counter-regulatory glucagon and differed between cohorts, and their expression at 24 h suggests miRNAs may potentiate and prolong the physiological response. Trial registration: ClinicalTrials.gov NCT03102801. MDPI 2022-11-24 /pmc/articles/PMC9736413/ /pubmed/36499023 http://dx.doi.org/10.3390/ijms232314696 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ramanjaneya, Manjunath
Bettahi, Ilham
Pawar, Krunal
Halabi, Najeeb M.
Moin, Abu Saleh Md
Sathyapalan, Thozhukat
Abou-Samra, Abdul Badi
Atkin, Stephen L.
Butler, Alexandra E.
MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
title MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
title_full MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
title_fullStr MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
title_full_unstemmed MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
title_short MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
title_sort microrna changes up to 24 h following induced hypoglycemia in type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736413/
https://www.ncbi.nlm.nih.gov/pubmed/36499023
http://dx.doi.org/10.3390/ijms232314696
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