Glut4 is upregulated despite decreased insulin signaling during prolonged fasting in northern elephant seal pups.
Postprandial cellular glucose uptake is dependent on an insulin-signaling cascade in muscle and adipose tissue, resulting in the translocation of the insulin-dependent glucose transporter 4 (Glut4) into the plasma membrane. Additionally, extended food deprivation is characterized by suppressed insulin signaling and decreased Glut4 expression. Northern elephant seals are adapted to prolonged fasts characterized by high levels of plasma glucose. To address the hypothesis that the fasting-induced decrease in insulin is associated with reduced insulin signaling in prolonged fasted seals, we compared the adipose protein levels of the cellular insulin-signaling pathway, Glut4 and plasma glucose, insulin, cortisol, and adiponectin concentrations between Early (n = 9; 2-3 wks postweaning) and Late (n = 8; 6-8 wks postweaning) fasted seals. Plasma adiponectin (230 ± 13 vs. 177 ± 11 ng/ml), insulin (2.7 ± 0.4 vs. 1.0 ± 0.1 μU/ml), and glucose (9.8 ± 0.5 vs. 8.0 ± 0.3 mM) decreased, while cortisol (124 ± 6 vs. 257 ± 30 nM) doubled with fasting. Glut4 increased (31%) with fasting despite the significant decreases in the cellular content of phosphatidylinositol 3-kinase as well as phosphorylated insulin receptor, insulin receptor substrate-1, and Akt2. Increased Glut4 may have contributed to the decrease in plasma glucose, but the decrease in insulin and insulin signaling suggests that Glut4 is not insulin-dependent in adipose tissue during prolonged fasting in elephant seals. The reduction of plasma glucose independent of insulin may make these animals an ideal model for the study of insulin resistance.
Viscarra
Jose A
JA
University of California, Merced, 95343, USA. jviscarra@ucmerced.edu
Vázquez-Medina
José Pablo
JP
Crocker
Daniel E
DE
Ortiz
Rudy M
RM
D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000378:metabolism; D046048:Seals, Earless / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
D052242:Adiponectin; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D006854:Hydrocortisone