Plasma DNA and deoxyribonuclease are associated with glucose metabolism in healthy mice

It is currently unknown why obesity leads in some patients to prediabetes and metabolic syndrome. Microinflammation potentially caused by extracellular DNA is supposed to be involved. The aim of this cross-sectional study in healthy mice was to analyze the association between plasma extracellular DN...

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Veröffentlicht in:PloS one 2022-04, Vol.17 (4), p.e0265099-e0265099
Hauptverfasser: Kmeťová, Katarína, Čonka, Jozef, Janko, Jakub, Illés, Júlia, Uličná, Oľga, Celec, Peter
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container_title PloS one
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Čonka, Jozef
Janko, Jakub
Illés, Júlia
Uličná, Oľga
Celec, Peter
description It is currently unknown why obesity leads in some patients to prediabetes and metabolic syndrome. Microinflammation potentially caused by extracellular DNA is supposed to be involved. The aim of this cross-sectional study in healthy mice was to analyze the association between plasma extracellular DNA and glucose metabolism. Fasting glycemia and insulin were measured in healthy adult female mice that subsequently underwent an oral glucose tolerance test. Indices of glucose metabolism and insulin sensitivity were calculated. DNA was isolated from plasma and quantified fluorometrically. Deoxyribonuclease (DNase) activity of plasma was measured using the single radial enzyme diffusion method. Fasting glycemia correlated negatively with both, extracellular DNA and DNase (r = -0.44 and r = -0.32, respectively). DNase was associated positively with the incremental area under curve (r = 0.35), while extracellular DNA correlated negatively with total area under curve of glycemia during oral glucose tolerance test (r = -0.34). Measures of insulin sensitivity were found to be associated with neither extracellular DNA, nor DNase. The hypothesis of an association of low DNase with increased fasting glucose was partially proved. Surprisingly, low extracellular DNA is associated with higher fasting glucose and lower glucose tolerance in mice. As novel therapeutic targets for prediabetes and metabolic syndrome are highly needed, this study provides novel unexpected associations within the limitations of the focus on physiological variability as it was conducted on healthy mice. The causality of these associations should be proved in further interventional experiments.
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Microinflammation potentially caused by extracellular DNA is supposed to be involved. The aim of this cross-sectional study in healthy mice was to analyze the association between plasma extracellular DNA and glucose metabolism. Fasting glycemia and insulin were measured in healthy adult female mice that subsequently underwent an oral glucose tolerance test. Indices of glucose metabolism and insulin sensitivity were calculated. DNA was isolated from plasma and quantified fluorometrically. Deoxyribonuclease (DNase) activity of plasma was measured using the single radial enzyme diffusion method. Fasting glycemia correlated negatively with both, extracellular DNA and DNase (r = -0.44 and r = -0.32, respectively). DNase was associated positively with the incremental area under curve (r = 0.35), while extracellular DNA correlated negatively with total area under curve of glycemia during oral glucose tolerance test (r = -0.34). 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Microinflammation potentially caused by extracellular DNA is supposed to be involved. The aim of this cross-sectional study in healthy mice was to analyze the association between plasma extracellular DNA and glucose metabolism. Fasting glycemia and insulin were measured in healthy adult female mice that subsequently underwent an oral glucose tolerance test. Indices of glucose metabolism and insulin sensitivity were calculated. DNA was isolated from plasma and quantified fluorometrically. Deoxyribonuclease (DNase) activity of plasma was measured using the single radial enzyme diffusion method. Fasting glycemia correlated negatively with both, extracellular DNA and DNase (r = -0.44 and r = -0.32, respectively). DNase was associated positively with the incremental area under curve (r = 0.35), while extracellular DNA correlated negatively with total area under curve of glycemia during oral glucose tolerance test (r = -0.34). Measures of insulin sensitivity were found to be associated with neither extracellular DNA, nor DNase. The hypothesis of an association of low DNase with increased fasting glucose was partially proved. Surprisingly, low extracellular DNA is associated with higher fasting glucose and lower glucose tolerance in mice. As novel therapeutic targets for prediabetes and metabolic syndrome are highly needed, this study provides novel unexpected associations within the limitations of the focus on physiological variability as it was conducted on healthy mice. The causality of these associations should be proved in further interventional experiments.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35385497</pmid><doi>10.1371/journal.pone.0265099</doi><tpages>e0265099</tpages><orcidid>https://orcid.org/0000-0001-5883-3580</orcidid><orcidid>https://orcid.org/0000-0002-2730-4587</orcidid><oa>free_for_read</oa></addata></record>
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subjects Analysis
Animals
Biology and life sciences
Blood glucose
Blood Glucose - metabolism
Cholesterol
Cross-Sectional Studies
Deoxyribonuclease
Deoxyribonucleases - blood
Deoxyribonucleic acid
Diffusion rate
DNA
DNA - blood
Fasting
Female
Genetic aspects
Glucose
Glucose metabolism
Glucose tolerance
Insulin
Insulin - metabolism
Insulin resistance
Insulin Resistance - physiology
Laboratory testing
Liver
Medical screening
Medicine
Medicine and Health Sciences
Metabolic disorders
Metabolic Syndrome
Mice
Mitochondrial DNA
Obesity
Physical Sciences
Physiological aspects
Plasma
Prediabetic State
Research and Analysis Methods
Sensitivity
Statistical analysis
Therapeutic targets
Weight control
title Plasma DNA and deoxyribonuclease are associated with glucose metabolism in healthy mice
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