| First Author | Li L | Year | 2019 |
| Journal | Diabetes | Volume | 68 |
| Issue | 12 | Pages | 2272-2286 |
| PubMed ID | 31537525 | Mgi Jnum | J:282294 |
| Mgi Id | MGI:6378632 | Doi | 10.2337/db19-0131 |
| Citation | Li L, et al. (2019) Metabolomics Identifies a Biomarker Revealing In Vivo Loss of Functional beta-Cell Mass Before Diabetes Onset. Diabetes 68(12):2272-2286 |
| abstractText | Identification of individuals with decreased functional beta-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic beta-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 beta-cell mass in the asymptomatic prediabetes stage. Nontargeted and targeted metabolomics were applied in both lean beta-Phb2(-/-) (beta-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 beta-cell mass promoting progressive diabetes development. Nontargeted metabolomics on beta-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 beta-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 beta-cell mass and uncovered metabolic similarities between liver and plasma, providing insights into the systemic effects caused by early decline in beta-cells. |
