Metabolomics identifies a biomarker revealing in vivo loss of functional ß-cell mass before diabetes onset

Article Article scientifique Article Metabolomics identifies a biomarker revealing in vivo loss of functional ß-cell mass before diabetes onset eng 2019 author Li Lingzi 813645 author Krznar Petra author Erban Alexander author Agazzi Andréa 813115 author Martin-Levilain Juliette 809819 author Supale Sachin 668430 author Kopka Joachim author Zamboni Nicola author Maechler Pierre 0000-0002-2005-1433 76515 2272-2286 10.2337/db19-0131 31537525 0012-1797 https://diabetes.diabetesjournals.org/content/68/12/2272.long Identification of pre-diabetic individuals with decreased functional ß-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic ß-cell defect remains unsuccessful. Metabolomics emerged as a powerful tool in providing read-outs of early disease states before clinical manifestation. We aimed at identifying novel plasma biomarkers for loss of functional ß-cell mass in the asymptomatic pre-diabetic stage. Non-targeted and targeted metabolomics were applied on both lean ß-Phb2-/- mice (ß-cell-specific prohibitin-2 knockout) and obese db/db mice (leptin receptor mutant), two distinct mouse models requiring neither chemical nor diet treatments to induce spontaneous decline of functional ß-cell mass promoting progressive diabetes development. Non-targeted metabolomics on ß-Phb2-/- mice identified 48 and 82 significantly affected metabolites in liver and plasma, respectively. Machine learning analysis pointed to deoxyhexose sugars consistently reduced at the asymptomatic pre-diabetic stage, including in db/db mice, showing strong correlation with the gradual loss of ß-cells. Further targeted metabolomics by GC-MS uncovered the identity of the deoxyhexose with 1,5-anhydroglucitol displaying the most significant changes. In conclusion, this study identified 1,5-anhydroglucitol associated with the loss of functional ß-cell mass and uncovered metabolic similarities between liver and plasma, providing insights into the systemic effects caused by early decline in ß-cells. Dewey 500.2 Dewey 612 Swiss National Science Foundation Sinergia #CRSII3_147637 CH 37 Département de physique théorique 133 134 Département de physiologie cellulaire et métabolisme 21C false 402 Mitochondries et métabolisme énergétique 671 Diabetes 68 12 64950b6a-8b4e-48d1-bb04-63a8ff3f152f Article (Accepted version) Public db19-0131.full.pdf 6688840 application/pdf openAccess Faculté des sciences / Section de physique / Département de physique théorique Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme

Title	Published in	Year	Views	Downloads

Metabolomics identifies a biomarker revealing in vivo loss of functional ß-cell mass before diabetes onset	Diabetes	2019	326	930
Large Deviations Theory for Chemical Reaction Networks		2017	693	441

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Agazzi, Andréa