A complete profile of carbohydrate metabolism during prolonged fasting in the northern elephant seal

Abstract

Glucose production is typically suppressed while fasting to facilitate protein sparing by avoiding the commitment of amino acids to gluconeogenesis. Previous work in fasting northern elephant seals, however, has found elevated rates of glucose production. To explore carbohydrate metabolism during prolonged fasting, we used a tracer technique utilizing D2O, [U‐13C]propionate, and [1,6‐13C]glucose. Nuclear magnetic resonance (NMR) was used to measure the abundance of each resulting positional isotope of glucose. We used the relative peak heights from the NMR spectra to quantify the rate of glucose production, the contribution of major gluconeogenic precursors to glucose production, the flux through the tricarboxylic‐acid cycle, and the activity of the phosphoenolpyruvate (PEP) cycle. Rates of glucose production closely agreed with previously measured values in this species. The combined contribution of glycogen and glycerol to gluconeogenesis was low, less than 10% of glucose production. The balance of glucose flux, greater than 90%, derived from PEP. The significant contribution of PEP to glucose production is consistent with high rates of carbon recycling through three‐carbon intermediates such as lactate. This is the first use of this positional isotope technique in a free‐ranging animal and provides the first comprehensive carbohydrate metabolism profile of an animal undertaking a prolonged fast.