Hyperpolarized Dihydroxyacetone Is a Sensitive Probe of Hepatic Gluconeogenic State

Type II diabetes and pre-diabetes are widely prevalent among adults. Elevated serum glucose levels are commonly treated by targeting hepatic gluconeogenesis for downregulation. However, direct measurement of hepatic gluconeogenic capacity is accomplished only via tracer metabolism approaches that rely on multiple assumptions, and are clinically intractable due to expense and time needed for the studies. We previously introduced hyperpolarized (HP) [2-C-13]dihydroxyacetone (DHA) as a sensitive detector of gluconeogenic potential, and showed that feeding and fasting produced robust changes in the ratio of detected hexoses (6C) to trioses (3C) in the perfused liver. To confirm that this ratio is robust in the setting of treatment and hormonal control, we used ex vivo perfused mouse livers from BLKS mice (glucagon treated and metformin treated), and db/db mice. We confirm that the ratio of signal intensities of 6C to 3C in C-13 nuclear magnetic resonance spectra post HP DHA administration is sensitive to hepatic gluconeogenic state. This method is directly applicable in vivo and can be implemented with existing technologies without the need for substantial modifications.

Automated summary

Type II diabetes and pre-diabetes are common in adults and are often treated by targeting hepatic gluconeogenesis. Direct measurement of hepatic gluconeogenic capacity is difficult, but the study successfully used hyperpolarized [2-C-13]dihydroxyacetone (DHA) to detect changes in gluconeogenic potential. Using ex vivo perfused mouse livers, the study confirmed that the ratio of signal intensities of 6C to 3C in C-13 nuclear magnetic resonance spectra is sensitive to hepatic gluconeogenic state.