Submitted on December 27, 2006
Accepted on February 28, 2007
Postpartum glycemic homeostasis in early lactating rats is accompanied by transient and specific increase of soleus insulin response through IRS2/AKT pathway
Gabriel Forato Anhê1, Sandro M Hirabara1, Tatiana C Turrer2, Luciana C Caperuto2, Fernando Forato Anhê3, Luciene Maria Ribeiro3, Anderson C Marçal1, Carla Roberta Oliveira Carvalho3, Rui Curi4, Ubiratan Fabres Machado3, and Silvana Bordin1*
1 Physiology and Biophysics, University of Sao Paulo - Institute of Biomedical Sciences, Sao Paulo, SP, Brazil
2 Physiology and Biophysics, University of Sao Paulo - Institute of Biomedical Sciences, SP, Brazil
3 Physiology and Biophysics, University of Sao Paulo - Institute of Biomedical Sciences, São Paulo, SP, Brazil
4 Physiology and Biophysics, University of Sao Paulo - Institute of Biomedical Sciences, São Paulo, Brazil
* To whom correspondence should be addressed. E-mail: sbordin{at}icb.usp.br.
It is known that, at the moment of the delivery, the immediate lost of the conceptus (the 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 of the studies concerning insulin sensitivity in lactating rats were carried out at 11-13 days postpartum and did not describe the functional changes in insulin response in early lactation. Here we show that the lactation hypersensitivity to insulin is observed as early as three 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. The response of soleus muscle was accompanied by an increase in GLUT4 content at L3. This adaptative 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. IRS2 tyrosine phosphorylation and its association with PI3-Kinase were also upregulated in soleus muscle. In parallel, PTP1B 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 the achievement of glucose homeostasis at the postpartum.
