Glucose production and substrate cycle activity in a fasting adapted animal, the northern elephant seal

Abstract

During prolonged fasting physiological mechanisms defend lean tissue from catabolism. In the fasting state, glucose is derived solely from gluconeogenesis, requiring some catabolism of amino acids for gluconeogenic substrates. This creates a conflict in animals undergoing fasts concurrently with metabolically challenging activities. This study investigated glucose metabolism in fasting and developing neonatal elephant seals. Glucose production and glucose cycle activity were measured early (2 weeks) and late (6 weeks) in the postweaning fasting period. Additionally the role of regulatory hormones on glucose production and glucose cycle activity were investigated. Glucose cycle activity was highly variable throughout the study period, did not change over the fasting period, and was not correlated with insulin or glucagon level. Endogenous glucose production (EGP) was 2.80±0.65·mg·kg -1 ·min -1 early and 2.21±0.12 during late fasting. Insulin to glucagon molar ratio decreased while cortisol levels increased over the fast (t=5.27, 2.84; P=0.003, 0.04; respectively). There was no relationship between EGP and hormone levels. The glucose production values measured in this study were high and exceeded the estimated gluconeogenic substrate available. These data suggest extensive glucose recycling via Cori cycle activity occurring in northern elephant seals, and we propose a possible justification for this recycling.

Variation in adrenal and thyroid hormones with life-history stage in juvenile northern elephant seals (Mirounga angustirostris)

“…Previous studies have demonstrated dramatic increases in serum cortisol concentrations during fasting duration in weaned pups and lactating females (Champagne et al, 2005;Ortiz et al, 2001). This pattern was thought to reflect increased needs for lipolysis during lactation and development (Fowler et al, 2016).…”

“…All assays have been validated for use in elephant seals (Champagne et al, , 2005Ensminger et al, 2014;Ortiz et al, 2001). Mean intra-assay CV% were <3.5% and mean inter-assay CV% were <5.6% for all analytes.…”

Hormone and metabolite changes associated with extended breeding fasts in male northern elephant seals (Mirounga angustirostris)

“…The greater loss of lean tissue in breeding male elephant seals relative to that observed in post-molt, fasting weanlings (Houser and Costa, 2001) and simultaneously fasting and lactating females (Crocker et al, 1998) may support this proposition provided lean tissue catabolism supports gluconeogenesis. However, high rates of glucose recycling, as suggested in weaned pups and lactating females (Champagne et al, 2005;, may reduce impacts of GH suppression on commitment of amino acids to glucose production.…”

“…Observations in weaned elephant seal pups suggest that declining I/G ratios while fasting result from increased glucagon levels coupled with either declining or stable insulin levels (Ortiz et al, 2003;Champagne et al, 2005). In contrast, lactating female elephant seals achieve reductions in I/G ratios while fasting through suppression of insulin alone (Champagne et al, 2006;Houser et al, 2007).…”

“…Each assay had been validated previously for use with northern elephant seal samples (Houser and Costa, 2001;Ortiz et al, 2001aOrtiz et al, , 2001bOrtiz et al, , 2003Champagne et al, 2005). Recognizing that the leptin antibody was raised against human leptin and that human leptin standards were used in the assay, immunoreactive NES leptin concentrations are expressed in ng mL − 1 human equivalents (ng mL − 1 HE) as previously reported (Ortiz et al, 2001a(Ortiz et al, , 2001b.…”