Glut4 Increases with Prolonged Fasting in Northern Elephant Seals

Abstract

The northern elephant seal (Mirounga angustirostris) experiences periods of prolonged fasting (2‐3 months) as part of its natural life history during which plasma glucose concentrations decrease despite the maintenance of relatively low plasma insulin. Cellular glucose metabolism is regulated by the insulin‐dependent glucose transport protein, Glut 4. Mechanisms of cellular glucose metabolism regulation have not been examined in fasting seals. Therefore, the effects of prolonged fasting on Glut4 and insulin receptor protein content, and plasma glucose were examined. Muscle and 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 fasting period: early (2 weeks) and late (6 to 8 weeks). Tissue samples were analyzed by Western blot for Glut4 and insulin receptor protein content. Circulating glucose levels decreased during the fast (9.8 ± 0.5 vs 8.0 ± 0.3 mM). In contrast, mean Glut4 levels increased in both muscle (31%) and blubber (26%) during the fast. Mean blubber insulin receptor content decreased 14% with the fast suggesting that the increase in Glut4 protein content is not insulin‐dependent during the fast in seals, which is consistent with the reduced circulating levels of insulin that we have reported for this species. Furthermore, the increase in Glut4 protein content may represent increased tissue utilization of glucose, which may partially explain the decrease in circulating levels. Funded by UC startup funds.