Increased AMPK Activity Compensates for Reduced Insulin Sensitivity During Prolonged Fasting in Northern Elephant Seal Pups

The northern elephant seal endures a 2–3 month fast during which it experiences sustained hyperglycemia, hypoglycemia and increased plasma cortisol and free fatty acids, conditions often seen in insulin resistant humans. The contribution of AMPK to the translocation of Glut4 during prolonged fasting, insulin‐resistant conditions is not well described. To address this, we performed a glucose tolerance test on early (n=5) and late (n=8) fasted elephant seal pups and compared the expression of insulin signaling proteins as well as PPARγ and AMPK in adipose. In addition, plasma insulin and adiponectin, and blood glucose were measured. Fasting was associated with decreased glucose clearance (as determined by the slope of blood glucose during the GTT), plasma insulin and adiponectin, and intracellular insulin signaling suggesting that fasting seals develop insulin resistance late in the fast. The expression of Glut4 and VAMP2 increased with fasting but did not change significantly in response to the GTT. PPARγ decreased with fasting but increased 73% in response to the GTT. Phosphorylated AMPK increased 50% suggesting that AMPK activity is increased in response to glucose late in the fast. The association between increased AMPK activity and Glut4 suggests that AMPK may compensate for the reduction in insulin signaling in the prolong‐fasted seals. Funded by NIH HL91767.