Tracking the carbons supplying gluconeogenesis

• Published in: The Journal of biological chemistry Vol. 295; no. 42; pp. 14419 - 14429
• Main Authors: Shah, Ankit M., Wondisford, Fredric E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.10.2020; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Carbon - metabolism; carbon flux; Carbon Isotopes - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Gluconeogenesis; Glucose - metabolism; Glycogen - metabolism; Humans; Hyperglycemia - metabolism; Hyperglycemia - pathology; isotopic tracer; JBC Reviews; mass spectrometry (MS); Metabolomics; nuclear magnetic resonance (NMR); type 2 diabetes; carbon flux; type 2 diabetes; metabolomics; nuclear magnetic resonance (NMR); gluconeogenesis; isotopic tracer; mass spectrometry (MS)
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.REV120.012758

As the burden of type 2 diabetes mellitus (T2DM) grows in the 21st century, the need to understand glucose metabolism heightens. Increased gluconeogenesis is a major contributor to the hyperglycemia seen in T2DM. Isotope tracer experiments in humans and animals over several decades have offered insights into gluconeogenesis under euglycemic and diabetic conditions. This review focuses on the current understanding of carbon flux in gluconeogenesis, including substrate contribution of various gluconeogenic precursors to glucose production. Alterations of gluconeogenic metabolites and fluxes in T2DM are discussed. We also highlight ongoing knowledge gaps in the literature that require further investigation. A comprehensive analysis of gluconeogenesis may enable a better understanding of T2DM pathophysiology and identification of novel targets for treating hyperglycemia.