Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes

Jumana Y Al-Aama,1,2 Hadiah B Al Mahdi,1 Mohammed A Salama,1 Khadija H Bakur,1,2 Amani Alhozali,3 Hala H Mosli,3 Suhad M Bahijri,4 Ahmed Bahieldin,5,6 Lothar Willmitzer,7 Sherif Edris1,5,6 1King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorde...

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Autores principales: Al-Aama JY, Al Mahdi HB, Salama MA, Bakur KH, Alhozali A, Mosli HH, Bahijri SM, Bahieldin A, Willmitzer L, Edris S
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:79189e4935ce49fea4c9ae46661825882021-12-02T04:48:38ZDetection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes1178-7007https://doaj.org/article/79189e4935ce49fea4c9ae46661825882019-12-01T00:00:00Zhttps://www.dovepress.com/detection-of-secondary-metabolites-as-biomarkers-for-the-early-diagnos-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Jumana Y Al-Aama,1,2 Hadiah B Al Mahdi,1 Mohammed A Salama,1 Khadija H Bakur,1,2 Amani Alhozali,3 Hala H Mosli,3 Suhad M Bahijri,4 Ahmed Bahieldin,5,6 Lothar Willmitzer,7 Sherif Edris1,5,6 1King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSA; 2King Abdulaziz University Faculty of Medicine, Department of Genetic Medicine, Jeddah, KSA; 3King Abdulaziz University, Faculty of Medicine, Department of Endocrinology and Metabolism, Jeddah, KSA; 4King Abdulaziz University, Faculty of Medicine, Department of Clinical Biochemistry, Jeddah, KSA; 5King Abdulaziz University, Faculty of Science, Biological Sciences Department, Jeddah, KSA; 6Ain Shams University, Department of Genetics, Cairo, Egypt; 7Max-Planck-Institut Für Molekulare Pflanzenphysiologie, Molecular Physiology, Golm, DE, GermanyCorrespondence: Sherif Edris; Jumana Y Al-AamaKing Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSATel +966 593 66 23 84Email seedris@kau.edu.sa; jalama@kau.edu.saBackground: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D.Methods: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC.Results: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely “glucagon signaling”, “glycine, serine and threonine” and “bile secretion”. Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study.Conclusion: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.Keywords: glucagon signaling, glycine production, bile secretion, insulin sensitivity/resistanceAl-Aama JYAl Mahdi HBSalama MABakur KHAlhozali AMosli HHBahijri SMBahieldin AWillmitzer LEdris SDove Medical Pressarticleglucagon signalingglycine productionbile secretioninsulin sensitivity/resistanceSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 2675-2684 (2019)
institution DOAJ
collection DOAJ
language EN
topic glucagon signaling
glycine production
bile secretion
insulin sensitivity/resistance
Specialties of internal medicine
RC581-951
spellingShingle glucagon signaling
glycine production
bile secretion
insulin sensitivity/resistance
Specialties of internal medicine
RC581-951
Al-Aama JY
Al Mahdi HB
Salama MA
Bakur KH
Alhozali A
Mosli HH
Bahijri SM
Bahieldin A
Willmitzer L
Edris S
Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes
description Jumana Y Al-Aama,1,2 Hadiah B Al Mahdi,1 Mohammed A Salama,1 Khadija H Bakur,1,2 Amani Alhozali,3 Hala H Mosli,3 Suhad M Bahijri,4 Ahmed Bahieldin,5,6 Lothar Willmitzer,7 Sherif Edris1,5,6 1King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSA; 2King Abdulaziz University Faculty of Medicine, Department of Genetic Medicine, Jeddah, KSA; 3King Abdulaziz University, Faculty of Medicine, Department of Endocrinology and Metabolism, Jeddah, KSA; 4King Abdulaziz University, Faculty of Medicine, Department of Clinical Biochemistry, Jeddah, KSA; 5King Abdulaziz University, Faculty of Science, Biological Sciences Department, Jeddah, KSA; 6Ain Shams University, Department of Genetics, Cairo, Egypt; 7Max-Planck-Institut Für Molekulare Pflanzenphysiologie, Molecular Physiology, Golm, DE, GermanyCorrespondence: Sherif Edris; Jumana Y Al-AamaKing Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSATel +966 593 66 23 84Email seedris@kau.edu.sa; jalama@kau.edu.saBackground: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D.Methods: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC.Results: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely “glucagon signaling”, “glycine, serine and threonine” and “bile secretion”. Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study.Conclusion: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.Keywords: glucagon signaling, glycine production, bile secretion, insulin sensitivity/resistance
format article
author Al-Aama JY
Al Mahdi HB
Salama MA
Bakur KH
Alhozali A
Mosli HH
Bahijri SM
Bahieldin A
Willmitzer L
Edris S
author_facet Al-Aama JY
Al Mahdi HB
Salama MA
Bakur KH
Alhozali A
Mosli HH
Bahijri SM
Bahieldin A
Willmitzer L
Edris S
author_sort Al-Aama JY
title Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes
title_short Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes
title_full Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes
title_fullStr Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes
title_full_unstemmed Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes
title_sort detection of secondary metabolites as biomarkers for the early diagnosis and prevention of type 2 diabetes
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/79189e4935ce49fea4c9ae4666182588
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