Plasma triacylglycerols are biomarkers of β-cell function in mice and humans
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Objectives: To find plasma biomarkers prognostic of type 2 diabetes, which could also inform on pancreatic β-cell deregulations or defects in the function of insulin target tissues. Methods: We conducted a systems biology approach to characterize the plasma lipidomes of C57Bl/6J, DBA/2J, and BALB/cJ mice under different nutritional conditions, as well as their pancreatic islet and liver transcriptomes. We searched for correlations between plasma lipids and tissue gene expression modules. Results: We identified strong correlation between plasma triacylglycerols (TAGs) and islet gene modules that comprise key regulators of glucose- and lipid-regulated insulin secretion and of the insulin signaling pathway, the two top hits were Gck and Abhd6 for negative and positive correlations, respectively. Correlations were also found between sphingomyelins and islet gene modules that overlapped in part with the gene modules correlated with TAGs. In the liver, the gene module most strongly correlated with plasma TAGs was enriched in mRNAs encoding fatty acid and carnitine transporters as well as multiple enzymes of the β-oxidation pathway. In humans, plasma TAGs also correlated with the expression of several of the same key regulators of insulin secretion and the insulin signaling pathway identified in mice. This cross-species comparative analysis further led to the identification of PITPNC1 as a candidate regulator of glucose-stimulated insulin secretion. Conclusion: TAGs emerge as biomarkers of a liver-to-β-cell axis that links hepatic β-oxidation to β-cell functional mass and insulin secretion.
Details
Original language | English |
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Article number | 101355 |
Journal | Molecular metabolism |
Volume | 54 |
Publication status | Published - Dec 2021 |
Peer-reviewed | Yes |
External IDs
PubMed | 34634522 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- Biomarkers, PITPNC1, Systems biology, Triacylglycerols, Type 2 diabetes, β-cell function