Increased intracellular Ca²⁺ concentrations prevent membrane localization of PH domains through the formation of Ca²⁺-phosphoinositides.

ABSTRACT: Insulin resistance, a key etiological factor in metabolic syndrome, is closely linked to ectopic lipid accumulation and increased intracellular Ca²⁺ concentrations in muscle and liver. However, the mechanism by which dysregulated intracellular Ca²⁺ homeostasis causes insulin resistance remains elusive. Here, we show that increased intracellular Ca²⁺ acts as a negative regulator of insulin signaling. Chronic intracellular Ca²⁺ overload in hepatocytes during obesity and hyperlipidemia attenuates the phosphorylation of protein kinase B (Akt) and its key downstream signaling molecules by inhibiting membrane localization of pleckstrin homology (PH) domains. Pharmacological approaches showed that elevated intracellular Ca²⁺ inhibits insulin-

SUBMITTER: Kang JK 

PROVIDER: S-EPMC5692539 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature