Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

Leandro Pereira De Moura,Maria Alice Rostom De Melo,Claudio Teodoro De Souza,Adelino Sanchez Ramos Da Silva,Eduardo Rochete Ropelle,Luciana Santos Souza Pauli,Rodolfo Marinho,Dennys Esper Cintra,José Rodrigo Pauli

doi:10.1186/1742-4933-10-8

Abstract

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging.

Highlights

Aging in both humans and rodents is associated with increased fasting and postprandial plasma insulin levels [1,2] and decreased in glucose tolerance [2,3] suggesting an insulin-resistant state
The fasting plasma glucose concentrations were similar between the groups; serum insulin was higher in old rats (Old and old sedentary rats (Old) Exe), when compared with young rats (Figure 1C-1D)
We found significant impairment in the glucose disappearance rate (Kitt) in old mice at rest when compared with young mice

Summary

Introduction

Aging in both humans and rodents is associated with increased fasting and postprandial plasma insulin levels [1,2] and decreased in glucose tolerance [2,3] suggesting an insulin-resistant state. Dysregulation of hepatic glucose homeostasis in aging associated with obesity is mainly caused by increased gluconeogenesis. Great efforts have been directed to study the mechanism of insulin resistance in liver related with aging and obesity. In this scenario, protein tyrosine phosphatase 1B (PTP1B) has emerged as key phosphatase, induced by inflammation, that has been shown to be a negative regulator of the insulin signal transduction in insulin resistant states. PTP1B is a highly regarded target of the pharmaceutical industry in the treatment of these disorders [7]

Methods

Results

Conclusion