scholarly journals Direct effects of endocannabinoid receptor antagonism on the glucose transport system in insulin‐resistant skeletal muscle of the obese Zucker rat

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Katherine Ann Lindborg ◽  
Erik J Henriksen
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Transport System ◽  
Zucker Rat ◽  
Direct Effects ◽  
Receptor Antagonism ◽  
Insulin Resistant ◽  
Glucose Transport System ◽  
Obese Zucker Rat ◽  
Endocannabinoid Receptor

Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat

2003 ◽  
Vol 285 (1) ◽  
pp. E98-E105 ◽  
Author(s):  
Erik J. Henriksen ◽  
Mary K. Teachey ◽  
Zachary C. Taylor ◽  
Stephan Jacob ◽  
Arne Ptock ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Zucker Rat ◽  
Transport Activity ◽  
Insulin Resistant ◽  
Obese Zucker Rat ◽  
Cla Isomers ◽  
Muscle Glucose Transport

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9, trans-11-CLA (c9,t11-CLA) and trans-10, cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker ( fa/ fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced ( P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides ( r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.

ACE inhibition and glucose transport in insulinresistant muscle: roles of bradykinin and nitric oxide

1999 ◽  
Vol 277 (1) ◽  
pp. R332-R336 ◽  
Author(s):  
Erik J. Henriksen ◽  
Stephan Jacob ◽  
Tyson R. Kinnick ◽  
Erik B. Youngblood ◽  
Melanie B. Schmit ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Insulin Action ◽  
Metabolic Effects ◽  
Zucker Rats ◽  
Ang Ii ◽  
Zucker Rat ◽  
Insulin Resistant ◽  
Obese Zucker Rat

Acute administration of the angiotensin-converting enzyme (ACE) inhibitor captopril enhances insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat. The present study was designed to assess whether this effect is mediated by an increase in the nonapeptide bradykinin (BK), by a decrease in action of ANG II, or both. Obese Zucker rats (8–9 wk old) were treated for 2 h with either captopril (50 mg/kg orally), bradykinin (200 μg/kg ip), or the ANG II receptor (AT1 subtype) antagonist eprosartan (20 mg/kg orally). Captopril treatment enhanced in vitro insulin-stimulated (2 mU/ml) 2-deoxyglucose uptake in the epitrochlearis muscle by 22% (251 ± 7 vs. 205 ± 9 pmol ⋅ mg−1 ⋅ 20 min−1; P < 0.05), whereas BK treatment enhanced this variable by 18% (249 ± 15 vs. 215 ± 7 pmol ⋅ mg−1 ⋅ 20 min−1; P < 0.05). Eprosartan did not significantly modify insulin action. The BK-mediated increase in insulin action was completely abolished by pretreatment with either the specific BK-B2 receptor antagonist HOE 140 (200 μg/kg ip) or the nitric oxide synthase inhibitor N ω-nitro-l-arginine methyl ester (50 mg/kg ip). Collectively, these results indicate that the modulation of insulin action by BK likely underlies the metabolic effects of ACE inhibitors in the insulin-resistant obese Zucker rat. Moreover, this modulation of insulin action by BK is likely mediated through B2 receptors and by an increase in nitric oxide production and/or action in skeletal muscle tissue.

scholarly journals Altered Regulation of Contraction-Induced Akt/mTOR/p70S6k Pathway Signaling in Skeletal Muscle of the Obese Zucker Rat

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Anjaiah Katta ◽  
Sunil Kakarla ◽  
Miaozong Wu ◽  
Satyanarayana Paturi ◽  
Murali K. Gadde ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zucker Rats ◽  
Strongly Correlated ◽  
Zucker Rat ◽  
Muscle Adaptation ◽  
Insulin Resistant ◽  
Obese Zucker Rat ◽  
Regulation Of Contraction ◽  
Muscle Loading ◽  
Ribosomal S6 Kinase

Increased muscle loading results in the phosphorylation of the 70 kDa ribosomal S6 kinase (p70S6k), and this event is strongly correlated with the degree of muscle adaptation following resistance exercise. Whether insulin resistance or the comorbidities associated with this disorder may affect the ability of skeletal muscle to activate p70S6k signaling following an exercise stimulus remains unclear. Here, we compare the contraction-induced activation of p70S6k signaling in the plantaris muscles of lean and insulin resistant obese Zucker rats following a single bout of increased contractile loading. Compared to lean animals, the basal phosphorylation of p70S6k (Thr389;37.2% and Thr421/Ser424;101.4%), Akt (Thr308;25.1%), and mTOR (Ser2448;63.0%) was higher in obese animals. Contraction increased the phosphorylation of p70S6k (Thr389), Akt (Ser473), and mTOR (Ser2448) in both models however the magnitude and kinetics of activation differed between models. These results suggest that contraction-induced activation of p70S6k signaling is altered in the muscle of the insulin resistant obese Zucker rat.

Invited Review: Effects of acute exercise and exercise training on insulin resistance

2002 ◽  
Vol 93 (2) ◽  
pp. 788-796 ◽  
Author(s):  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Acute Exercise ◽  
Insulin Resistant ◽  
Beneficial Effects ◽  
Glucose Transport System

Insulin resistance of skeletal muscle glucose transport is a key defect in the development of impaired glucose tolerance and Type 2 diabetes. It is well established that both an acute bout of exercise and chronic endurance exercise training can have beneficial effects on insulin action in insulin-resistant states. This review summarizes the present state of knowledge regarding these effects in the obese Zucker rat, a widely used rodent model of obesity-associated insulin resistance, and in insulin-resistant humans with impaired glucose tolerance or Type 2 diabetes. A single bout of prolonged aerobic exercise (30–60 min at ∼60–70% of maximal oxygen consumption) can significantly lower plasma glucose levels, owing to normal contraction-induced stimulation of GLUT-4 glucose transporter translocation and glucose transport activity in insulin-resistant skeletal muscle. However, little is currently known about the effects of acute exercise on muscle insulin signaling in the postexercise state in insulin-resistant individuals. A well-established adaptive response to exercise training in conditions of insulin resistance is improved glucose tolerance and enhanced skeletal muscle insulin sensitivity of glucose transport. This training-induced enhancement of insulin action is associated with upregulation of specific components of the glucose transport system in insulin-resistant muscle and includes increased protein expression of GLUT-4 and insulin receptor substrate-1. It is clear that further investigations are needed to further elucidate the specific molecular mechanisms underlying the beneficial effects of acute exercise and exercise training on the glucose transport system in insulin-resistant mammalian skeletal muscle.

Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats

2001 ◽  
Vol 91 (1) ◽  
pp. 145-153 ◽  
Author(s):  
Vitoon Saengsirisuwan ◽  
Tyson R. Kinnick ◽  
Melanie B. Schmit ◽  
Erik J. Henriksen
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Insulin Action ◽  
Combined Treatment ◽  
Protein Carbonyl ◽  
Insulin Resistant ◽  
Glut 4 ◽  
Obese Zucker Rat ◽  
Muscle Glucose Transport

Exercise training (ET) or the antioxidant R(+)-α-lipoic acid (R-ALA) individually increases insulin action in the insulin-resistant obese Zucker rat. The purpose of the present study was to determine the interactions of ET and R-ALA on insulin action and oxidative stress in skeletal muscle of the obese Zucker rat. Animals either remained sedentary, received R-ALA (30 mg · kg body wt−1 · day−1), performed ET (treadmill running), or underwent both R-ALA treatment and ET for 6 wk. During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose (26–32%) and insulin (29–30%) responses compared with sedentary controls. R-ALA alone decreased (19%) the glucose-insulin index (indicative of increased insulin sensitivity), and this parameter was reduced (48–52%) to the greatest extent in the ET and combined treatment groups. ET or R-ALA individually increased insulin-mediated glucose transport activity in isolated epitrochlearis (44–48%) and soleus (37–57%) muscles. The greatest increases in insulin action in these muscles (80 and 99%, respectively) were observed in the combined treatment group. Whereas the improvement in insulin-mediated glucose transport in soleus due to R-ALA was associated with decreased protein carbonyl levels (an index of oxidative stress), improvement because of ET was associated with decreased protein carbonyls as well as enhanced GLUT-4 protein. However, there was no interactive effect of ET and R-ALA on GLUT-4 protein or protein carbonyl levels. These results indicate that ET and R-ALA interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscle. Because the further improvement in muscle glucose transport in the combined group was not associated with additional upregulation of GLUT-4 protein or a further reduction in oxidative stress, the mechanism for this interaction must be due to additional, as yet unidentified, factors.

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