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.

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.

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.

Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat

1996 ◽  
Vol 271 (2) ◽  
pp. E294-E301 ◽  
Author(s):  
G. J. Etgen ◽  
C. M. Wilson ◽  
J. Jensen ◽  
S. W. Cushman ◽  
J. L. Ivy
Keyword(s):  
Skeletal Muscle ◽  
Cell Surface ◽  
Glucose Transport ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Glut 4 ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Slow Twitch ◽  
Fast Twitch

The relationship between 3-O-methyl-D-glucose transport and 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1, 3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA)-labeled cell surface GLUT-4 protein was assessed in fast-twitch (epitrochlearis) and slow-twitch (soleus) muscles of lean and obese (fa/fa) Zucker rats. In the absence of insulin, glucose transport as well as cell surface GLUT-4 protein was similar in both epitrochlearis and soleus muscles of lean and obese rats. In contrast, insulin-stimulated glucose transport rates were significantly higher for lean than obese rats in both soleus (0.74 +/- 0.05 vs. 0.40 +/- 0.02 mumol.g-1.10 min-1) and epitrochlearis (0.51 +/- 0.05 vs. 0.17 +/- 0.02 mumol.g-1.10 min-1) muscles. The ability of insulin to enhance glucose transport in fast- and slow-twitch muscles from both lean and obese rats corresponded directly with changes in cell surface GLUT-4 protein. Muscle contraction elicited similar increases in glucose transport in lean and obese rats, with the effect being more pronounced in fast-twitch (0.70 +/- 0.07 and 0.77 +/- 0.04 mumol.g-1.10 min-1 for obese and lean, respectively) than in slow-twitch muscle (0.36 +/- 0.03 and 0.40 +/- 0.02 mumol.g-1.10 min-1 for obese and lean, respectively). The contraction-induced changes in glucose transport directly corresponded with the observed changes in cell surface GLUT-4 protein. Thus the reduced glucose transport response to insulin in skeletal muscle of the obese Zucker rat appears to result directly from an inability to effectively enhance cell surface GLUT-4 protein.

Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle

1993 ◽  
Vol 265 (2) ◽  
pp. R447-R452 ◽  
Author(s):  
P. A. King ◽  
J. J. Betts ◽  
E. D. Horton ◽  
E. S. Horton
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Plasma Membranes ◽  
Acute Exercise ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Rat Muscle ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
Muscle Glucose Transport

Insulin or exercise stimulates skeletal muscle glucose transport, most likely by increasing both the number and activity of glucose transporters in the plasma membrane. Skeletal muscle glucose transport of genetically obese Zucker rats (fa/fa) displays a severe insulin resistance that results, at least in part, from a failure of net transporter translocation to the cell membrane (King, P., E. D. Horton, M. Hirshman, and E. S. Horton. J. Clin, Invest. 90: 1568-1575, 1992). The purpose of the present study was to determine if the obese rat muscle was also resistant to the action of acute exercise to increase glucose transport and, if so, to determine if the defect involved transporter translocation as seen in the resistance to insulin. The muscle glucose transport system was investigated in plasma membranes isolated from postprandial, sedentary or acutely exercised, lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that an acute bout of exercise resulted in a threefold increase in the maximum velocity (Vmax) for lean animals (5.7 vs. 17.6 nmol.mg protein-1.min-1) and a 4.5-fold increase in the Vmax for obese rats (4.1 vs. 18.6 nmol.mg protein-1.min-1). For both lean and obese animals, this increase in transport was associated with an increase in transporter number measured by cytochalasin B binding (1.6- and 2.2-fold, respectively) and with an increase in the average carrier turnover number (1.9- and 2.0-fold, respectively). The results indicate that, unlike a maximal insulin stimulus, acute exercise of the obese Zucker rat promotes both transporter translocation and transporter activation in skeletal muscle.

scholarly journals The age-related increase in renal clusterin mRNA is accelerated in obese Zucker rats.

1998 ◽  
Vol 9 (1) ◽  
pp. 38-45 ◽  
Author(s):  
N J Laping ◽  
B A Olson ◽  
J R Day ◽  
B M Brickson ◽  
L C Contino ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Injury ◽  
Rat Kidney ◽  
Zucker Rats ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Age Related ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats ◽  
F344 Rats

Clusterin is a multifunctional glycoprotein associated with development and tissue injury. Because renal function decreases with advancing age in the obese Zucker rat, clusterin mRNA expression was examined in the kidney of young adult Zucker rats and compared with age-related changes in renal clusterin mRNA expression in Fischer 344 (F344) rats. Renal clusterin mRNA levels in the obese Zucker rat were 2.5-fold higher by 3 mo of age and fourfold higher at 5 mo of age compared with the lean strain. In comparison, renal clusterin mRNA in 12-mo-old F344 rats was twofold higher than in 3-mo-old animals and was tenfold higher at 24 mo of age. Clusterin mRNA was positively correlated with urinary protein excretion and negatively correlated with creatinine clearance in Zucker rats. Clusterin was increased in select nephrons of the obese Zucker rat kidney and in 24-mo-old F344 rat kidney as assessed by in situ hybridization. Increased expression of clusterin mRNA occurred mostly in the tubular epithelium of dilated, convoluted proximal tubules. These data indicate that renal clusterin mRNA levels increase as a function of age and that age-related increases in renal clusterin and the associated tubular abnormalities are accelerated in obese Zucker rats.

scholarly journals Mechanism controlling sleep organization of the obese Zucker rats

1998 ◽  
Vol 84 (1) ◽  
pp. 253-256 ◽  
Author(s):  
David Megirian ◽  
Jacek Dmochowski ◽  
Gaspar A. Farkas
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Zucker Rats ◽  
Rapid Eye Movement ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Mean

Megirian, David, Jacek Dmochowski, and Gaspar A. Farkas. Mechanism controlling sleep organization of the obese Zucker rat. J. Appl. Physiol. 84(1): 253–256, 1998.—We tested the hypothesis that the obese ( fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye-movement (REM) sleep states. Assessment of states was made with light present (1000–1600), at the rats thermoneutral temperature of 29°C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did ( P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different ( P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.

scholarly journals The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats

Diabetologia ◽  
2004 ◽  
Vol 47 (3) ◽  
pp. 412-419 ◽  
Author(s):  
G. D. Wadley ◽  
C. R. Bruce ◽  
N. Konstantopoulos ◽  
S. L. Macaulay ◽  
K. F. Howlett ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zucker Rats ◽  
Protein Abundance ◽  
Insulin Resistant ◽  
Obese Zucker Rats ◽  
Cbl Protein
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