Prolonged fasting suppresses cellular insulin‐dependent activity in adipose tissue of the northern elephant seal

Abstract

Throughout its life, the northern elephant seal (Mirounga angustirostris) experiences periods of prolonged fasting during which plasma glucose reaches hyperglycemic levels. As the fast progresses, the levels of circulating glucose decrease, despite relatively low or decreasing plasma insulin levels. Cellular glucose uptake is dependent on an insulin‐activated signaling cascade resulting in the translocation of the glucose transport protein, Glut4, into the plasma membrane. In order to understand how this pathway is affected by prolonged fasting PI3K, AKT and VAMP2 content, and plasma insulin were examined. Blubber biopsies as well as plasma samples were obtained from two groups of northern elephant seal pups (n = 10/group) sampled during their post weaning fast: early (2 weeks) and late (6 to 8 weeks). Tissue content of PI3K, AKT, and VAMP2 proteins was quantified by western blot. Plasma insulin did not change (1.5 ± 0.4 vs. 1.2 ± 0.2 uU/mL) between early and late fasting. While PI3K and VAMP2 also did not change, AKT decreased 29% with the fast. We have previously shown that fasting is associated with a decrease in insulin receptor (IR), but an increase in Glut 4. Because insulin stimulates PI3K and AKT, the decreases in insulin and IR may explain the lack of change in PI3K and the decrease in AKT suggesting that fasting suppresses cellular insulin‐dependent activity. Funded by NIH HL91767 and UC Startup funds.