Abstract
Objectives: The present study investigated the impact of voluntary exercise on insulin-stimulated glucose transport and the protein expression and phosphorylation status of the signaling molecules known to be involved in the glucose transport process in the soleus muscle as well as other cardiometabolic risks in a rat model with insulin resistance syndrome induced by chronic angiotensin II (ANGII) infusion.Materials and Methods: Male Sprague-Dawley rats were assigned to sedentary or voluntary wheel running (VWR) groups. Following a 6-week period, rats in each group were subdivided and subcutaneously administered either normal saline or ANGII at 100 ng/kg/min for 14 days. Blood pressure, glucose tolerance, insulin-stimulated glucose transport and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, c-Jun NH2-terminal kinase (JNK), p38 MAPK, angiotensin converting enzyme (ACE), ANGII type 1 receptor (AT1R), ACE2, Mas receptor (MasR) and oxidative stress marker in the soleus muscle, were evaluated.Results: Exercise protected against the insulin resistance of glucose transport and defective insulin signaling molecules in the soleus muscle; this effect was associated with a significant increase in AMPK Thr172 (43%) and decreases in oxidative stress marker (31%) and insulin-induced p38 MAPK Thr180/Tyr182 (45%) and SAPK/JNK Thr183/Tyr185 (25%), without significant changes in expression of AT1R, AT2R, ACE, ACE2, and MasR when compared to the sedentary rats given ANGII infusion. At the systemic level, VWR significantly decreased body weight, fat weight, and systolic blood pressure as well as improved serum lipid profiles.Conclusion: Voluntary exercise can alleviate insulin resistance of glucose transport and impaired insulin signaling molecules in the soleus muscle and improve whole-body insulin sensitivity in rats chronically administered with ANGII.
Highlights
Insulin resistance of skeletal muscle is the reduced ability of insulin to stimulate glucose uptake into skeletal muscle, the major site of glucose disposal
Rats given access to voluntary wheel running (VWR) showed an 8–9% lower (P < 0.001) final body weight that was accompanied by decreased abdominal fat weight-to-body weight ratio (P
We found that VWR enhanced the phosphorylation level of AMPK Thr172 in the soleus muscle of saline-infused rats (Figure 6A), while the impaired phosphorylation level of AMPK Thr172 induced by Angiotensin II (ANGII) infusion was not observed in the soleus muscle of rats that regularly exercised prior to ANGII infusion
Summary
Insulin resistance of skeletal muscle is the reduced ability of insulin to stimulate glucose uptake into skeletal muscle, the major site of glucose disposal. Skeletal muscle insulin resistance frequently occurs in parallel with other cardiometabolic risks including glucose intolerance, hyperinsulinemia, dyslipidemia, essential hypertension, and central obesity. Together, these multifaceted conditions are known as insulin resistance syndrome, a major risk factor of diabetes and cardiovascular diseases (Reaven, 2005; DeFronzo and Tripathy, 2009). The adverse effects of ANGII could be counteracted when the novel RAS pathway was enhanced via proteins in the ACE2/angiotensin-(1-7)/Mas receptor (MasR) axis (Santos et al, 2008; Prasannarong et al, 2012; Santos and Andrade, 2014). Activation of the ACE2/ANG-(1-7)/MasR axis led to an improvement in glucose and lipid metabolism (Ferrario et al, 2005; Santos et al, 2008, 2013; Prasannarong et al, 2012; Echeverria-Rodriguez et al, 2014; Santos and Andrade, 2014)
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