Gene interactions and pathways from curated databases and text-mining
Diabetologia 2006, PMID: 16489447

Leukaemia inhibitory factor stimulates glucose transport in isolated cardiomyocytes and induces insulin resistance after chronic exposure.

Florholmen, G; Thoresen, G H; Rustan, A C; Jensen, J; Christensen, G; Aas, V

OBJECTIVE

Hypertrophic and failing hearts have increased utilisation of glucose, but also develop insulin resistance and reduced ability to produce ATP. Increased levels of the IL-6-related cytokine leukaemia inhibitory factor (LIF) are found in failing hearts, and we have recently shown that LIF reduces ATP production in isolated cardiomyocytes. In the present study we investigated effects of LIF on glucose metabolism, and how LIF-treated cells respond to insulin stimulation.

METHODS

Cardiomyocytes were isolated from adult Wistar rats by collagen digestion, maintained in culture for 48 h, and then treated with 1 nmol/l LIF.

RESULTS

Acute LIF treatment increased deoxyglucose uptake compared with controls, but no additive effect was observed in cardiomyocytes treated with LIF and insulin. The phosphatidylinositol 3-kinase inhibitor wortmannin did not affect LIF-induced glucose uptake. LIF had no effect on AMP-activated protein kinase phosphorylation. Cardiomyocytes treated with LIF for 48 h did not respond to insulin by increasing deoxyglucose uptake and showed a reduced insulin-mediated uptake of oleic acid and formation of complex lipids compared with control cells. Chronic LIF treatment increased gene expression of the suppressor of cytokine signalling (Socs) 3 and reduced expression of solute carrier family 2, member 4 (Slc2a4, previously known as glucose transporter 4 [Glut4]). In line with these observations, chronic LIF treatment reduced insulin-mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase (GSK)-3.

CONCLUSIONS

Acute LIF treatment increased glucose uptake in isolated cardiomyocytes by a pathway different from that of insulin. Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin-mediated phosphorylation of GSK-3 and Akt/PKB.

Diseases/Pathways annotated by Medline MESH: Insulin Resistance
Document information provided by NCBI PubMed

Text Mining Data

Akt/protein → insulin: " In line with these observations, chronic LIF treatment reduced insulin mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase ( GSK ) -3 "

glycogen synthase kinase ( GSK ) → insulin: " In line with these observations, chronic LIF treatment reduced insulin mediated phosphorylation of both Akt/protein kinase B (PKB) and glycogen synthase kinase ( GSK ) -3 "

Akt/PKB ⊣ Slc2a4: " Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4 , and impaired insulin mediated phosphorylation of GSK-3 and Akt/PKB "

Akt/PKB ⊣ Socs3: " Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin mediated phosphorylation of GSK-3 and Akt/PKB "

Akt/PKB ⊣ Slc2a4: " Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4 , and impaired insulin mediated phosphorylation of GSK-3 and Akt/PKB "

Akt/PKB → insulin: " Chronic LIF treatment induced insulin resistance, possibly mediated by altered expression of Socs3 and Slc2a4, and impaired insulin mediated phosphorylation of GSK-3 and Akt/PKB "

Manually curated Databases

No curated data.