Metabolomics Identifies a Biomarker Revealing In Vivo Loss of Functional β-Cell Mass Before Diabetes Onset.

Published

Journal Article

Identification of individuals with decreased functional β-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic β-cell defect remains unsuccessful. Metabolomics has emerged as a powerful tool in providing readouts of early disease states before clinical manifestation. We aimed at identifying novel plasma biomarkers for loss of functional β-cell mass in the asymptomatic prediabetes stage. Nontargeted and targeted metabolomics were applied in both lean β-Phb2-/- (β-cell-specific prohibitin-2 knockout) mice and obese db/db (leptin receptor mutant) mice, two distinct mouse models requiring neither chemical nor dietary treatments to induce spontaneous decline of functional β-cell mass promoting progressive diabetes development. Nontargeted metabolomics on β-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 prediabetes stage, including in db/db mice, showing strong correlation with the gradual loss of β-cells. Further targeted metabolomics by gas chromatography-mass spectrometry uncovered the identity of the deoxyhexose, with 1,5-anhydroglucitol displaying the most substantial changes. In conclusion, this study identified 1,5-anhydroglucitol as associated with the loss of functional β-cell mass and uncovered metabolic similarities between liver and plasma, providing insights into the systemic effects caused by early decline in β-cells.

Full Text

Duke Authors

Cited Authors

  • Li, L; Krznar, P; Erban, A; Agazzi, A; Martin-Levilain, J; Supale, S; Kopka, J; Zamboni, N; Maechler, P

Published Date

  • December 2019

Published In

Volume / Issue

  • 68 / 12

Start / End Page

  • 2272 - 2286

PubMed ID

  • 31537525

Pubmed Central ID

  • 31537525

Electronic International Standard Serial Number (EISSN)

  • 1939-327X

International Standard Serial Number (ISSN)

  • 0012-1797

Digital Object Identifier (DOI)

  • 10.2337/db19-0131

Language

  • eng