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Postpartum glycemic homeostasis in early lactating rats is accompanied by transient and specific increase of soleus insulin response through IRS2/AKT pathway
Authors:Anhê Gabriel F  Hirabara Sandro M  Turrer Tatiana C  Caperuto Luciana C  Anhê Fernando F  Ribeiro Luciene M  Marçal Anderson C  Carvalho Carla R O  Curi Rui  Machado Ubiratan F  Bordin Silvana
Institution:Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S?o Paulo, S?o Paulo, SP, Brazil.
Abstract:It is known that at the moment of delivery immediate lost of conceptus (main site of glucose disposal in late pregnancy) is not able to disturb glucose homeostasis in early lactating mothers. However, the mechanism by which this adaptation takes place in early lactation is still unknown. Most studies concerning insulin sensitivity in lactating rats were carried out at 11-13 days postpartum and did not describe functional changes in insulin response in early lactation. Here we show that lactation hypersensitivity to insulin is observed as early as 3 days after delivery (L3). We show that the oxidative soleus muscle displays a transient increased maximal insulin-induced glucose uptake and CO2 production, which is temporally limited to L3. Response of soleus muscle was accompanied by an increase in glucose transporter 4 (GLUT4) content at L3. This adaptive response was not detected in the glycolytic plantaris muscle, which displayed lower content of GLUT4. We also found that soleus muscle from early lactating rats have higher insulin receptor expression and tyrosine phosphorylation. Downstream steps of insulin signaling pathway; e.g., insulin receptor substrate 2 tyrosine phosphorylation and its association with phosphatidylinositol 3-kinase were also upregulated in soleus muscle. In parallel, protein tyrosine phosphatase 1B expression, a negative regulator of insulin signal, was reduced. Importantly, all of these molecular alterations were time limited to L3 and were not observed in plantaris muscle. These results suggest that improved insulin action in oxidative, but not in glycolytic muscle might contribute to achievement of glucose homeostasis postpartum.
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