Palmitate acutely raises glycogen synthesis in rat soleus muscle by a mechanism that requires its metabolization (Randle cycle)

FEBS Letters

de Oliveira Carvalho, Carla Roberta¹  Mendonça, José Roberto¹  Curi, Rui¹  Piltcher Haber, Esther¹  Fernandes, Luiz Claudio²  Massao Hirabara, Sandro¹ 

[1] Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Cidade Universitária, Av. Professor Lineu Prestes 1524, Butantã, São Paulo, SP 05508-900, Brazil;Department of Physiology, Sector of Biological Sciences, Federal University of Paraná, Curitiba, PR 81530-900, Brazil

关键词: Palmitate;    Soleus muscle;    Glucose metabolism;    Glycogen synthesis;    Insulin signalling;    FFA;    free fatty acids;    GLUT-4;    glucose transporter-4;    IRS;    insulin receptor substrate;    MAP kinases;    mitogen-activated protein kinases;    PI3-K;    phosphatidylinositol 3-kinase;    PKB;    protein kinase B (also known as Akt);    PKC;    protein kinase C;   

DOI  :  10.1016/S0014-5793(03)00316-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The acute effect of palmitate on glucose metabolism in rat skeletal muscle was examined. Soleus muscles from Wistar male rats were incubated in Krebs–Ringer bicarbonate buffer, for 1 h, in the absence or presence of 10 mU/ml insulin and 0, 50 or 100 μM palmitate. Palmitate increased the insulin-stimulated [¹⁴C]glycogen synthesis, decreased lactate production, and did not alter D-[U-¹⁴C]glucose decarboxylation and 2-deoxy-D-[2,6-³H]glucose uptake. This fatty acid decreased the conversion of pyruvate to lactate and [1-¹⁴C]pyruvate decarboxylation and increased ¹⁴CO₂ produced from [2-¹⁴C]pyruvate. Palmitate reduced insulin-stimulated phosphorylation of insulin receptor substrate-1/2, Akt, and p44/42 mitogen-activated protein kinases. Bromopalmitate, a non-metabolizable analogue of palmitate, reduced [¹⁴C]glycogen synthesis. A strong correlation was found between [U-¹⁴C]palmitate decarboxylation and [¹⁴C]glycogen synthesis (r=0.99). Also, palmitate increased intracellular content of glucose 6-phosphate in the presence of insulin. These results led us to postulate that palmitate acutely potentiates insulin-stimulated glycogen synthesis by a mechanism that requires its metabolization (Randle cycle). The inhibitory effect of palmitate on insulin-stimulated protein phosphorylation might play an important role for the development of insulin resistance in conditions of chronic exposure to high levels of fatty acids.

【 授权许可】

Unknown