Activation of PKB and ERK, but not PI3K, is involved in fucosylated chondroitin sulphate from Acaudina molpadioides induced glucose uptake

Abstract

Fucosylated chondroitin sulphate from sea cucumber can mitigate hyperglycaemia. However, the possible mechanism is unclear. We investigated the effects of fucosylated chondroitin sulphate from Acaudina molpadioides (Am-CHS) on glucose uptake and its mechanism using TNF-α-induced 3T3-L1 insulin resistant adipocytes. Results showed that Am-CHS could significantly increase glucose uptake and GLUT4 translocation, and phosphorylated PI3K, PKB, and ERK. Am-CHS reversed MK2206-induced reduction in glucose uptake, GLUT4 translocation, and PKB phosphorylation. Am-CHS antagonized U0126-induced decrease in glucose uptake, GLUT4 translocation, and ERK1/2 phosphorylation. Am-CHS inhibited wortmannin-induced reduction in glucose uptake and GLUT4 translocation reduction. Wortmannin-restrained PKB and ERK1/2 phosphorylation was antagonized by Am-CHS, but the lowered PI3K phosphorylation remained unchanged. Am-CHS also lowered blood glucose, increased m-GLUT4, p-PKB (Ser473), p-ERK1/2, p-PI3K p85, and p-IRS-1 (Tyr612) expressions, and decreased p-PKB (Ser308) expression in adipose tissues of insulin resistant mice. These indicate that PKB and ERK activation are involved in Am-CHS-triggered glucose, but not PI3K.