5′AMP-activated Protein Kinase Activity is Increased in Adipose Tissue of Northern Elephant Seal Pups during Prolonged Fasting-Induced Insulin Resistance

• Published in: Journal of Endocrinology
• Main Authors: Viscarra, Jose A., Champagne, Cory D., Crocker, Daniel E., Ortiz, Rudy M.
• Format: Text
• Language: English
• Published: 2011
• Subjects: Article; Elephant Seal; Elephant Seals
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250370; http://www.ncbi.nlm.nih.gov/pubmed/21429964; https://doi.org/10.1530/JOE-11-0017

Northern elephant seals endure a 2–3 month fast characterized by sustained hyperglycemia, hypoinsulinemia and increased plasma cortisol and free fatty acids, conditions often seen in insulin resistant humans. We previously showed that adipose Glut4 expression and AMP kinase (AMPK) activity increase and plasma glucose decreases in fasting seals suggesting that AMPK activity contributes to glucose regulation during insulin resistant conditions. To address the hypothesis that AMPK activity increases during fasting-induced insulin resistance, we performed glucose tolerance tests (GTT) on early (n=5) and late (n=8) fasted seal pups and compared adipose tissue expression of insulin signaling proteins, PPARγ, and AMPK, in addition to plasma adiponectin, leptin, cortisol, insulin and non-esterified fatty acids (NEFA) levels. Fasting was associated with decreased glucose clearance, plasma insulin and adiponectin, and intracellular insulin signaling, as well as increased plasma cortisol and NEFAs, supporting the suggestion that seals develop insulin resistance late in the fast. Expression of Glut4 and VAMP2 increased (52% and 63%, respectively) with fasting but did not change significantly during the GTT. PPARγ and phosphorylated AMPK did not change in early fasted seals, but increased significantly (73% and 50%, respectively) in late fasted seals during the GTT. Increased AMPK activity along with the reduction in the activity of insulin-signaling proteins supports our hypothesis that AMPK activity is increased following the onset of insulin resistance. The association between increased AMPK activity and Glut4 expression suggests that AMPK plays a greater role in regulating glucose metabolism in mammals adapted to prolonged fasting than in non-fasting mammals.