scholarly journals Decreased skeletal muscle phosphotyrosine phosphatase (PTPase) activity towards insulin receptors in insulin-resistant Zucker rats measured by delayed Europium fluorescence

Diabetologia ◽  
1996 ◽  
Vol 39 (2) ◽  
pp. 142-148 ◽  
Author(s):  
D. Worm ◽  
A. Handberg ◽  
E. Hoppe ◽  
J. Vinten ◽  
H. Beck-Nielsen
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptors ◽  
Zucker Rats ◽  
Phosphotyrosine Phosphatase ◽  
Insulin Resistant ◽  
Ptpase Activity

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

Acute selective glycogen synthase kinase-3 inhibition enhances insulin signaling in prediabetic insulin-resistant rat skeletal muscle

2005 ◽  
Vol 288 (6) ◽  
pp. E1188-E1194 ◽  
Author(s):  
Betsy B. Dokken ◽  
Julie A. Sloniger ◽  
Erik J. Henriksen
Keyword(s):  
Skeletal Muscle ◽  
Tyrosine Phosphorylation ◽  
Glucose Transport ◽  
Insulin Signaling ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Serine Phosphorylation ◽  
Zucker Rats ◽  
Type I ◽  
Insulin Resistant

Glycogen synthase kinase-3 (GSK3) has been implicated in the multifactorial etiology of skeletal muscle insulin resistance in animal models and in human type 2 diabetic subjects. However, the potential molecular mechanisms involved are not yet fully understood. Therefore, we determined if selective GSK3 inhibition in vitro leads to an improvement in insulin action on glucose transport activity in isolated skeletal muscle of insulin-resistant, prediabetic obese Zucker rats and if these effects of GSK3 inhibition are associated with enhanced insulin signaling. Type I soleus and type IIb epitrochlearis muscles from female obese Zucker rats were incubated in the absence or presence of a selective, small organic GSK3 inhibitor (1 μM CT118637, Ki < 10 nM for GSK3α and GSK3β). Maximal insulin stimulation (5 mU/ml) of glucose transport activity, glycogen synthase activity, and selected insulin-signaling factors [tyrosine phosphorylation of insulin receptor (IR) and IRS-1, IRS-1 associated with p85 subunit of phosphatidylinositol 3-kinase, and serine phosphorylation of Akt and GSK3] were assessed. GSK3 inhibition enhanced ( P <0.05) basal glycogen synthase activity and insulin-stimulated glucose transport in obese epitrochlearis (81 and 24%) and soleus (108 and 20%) muscles. GSK3 inhibition did not modify insulin-stimulated tyrosine phosphorylation of IR β-subunit in either muscle type. However, in obese soleus, GSK3 inhibition enhanced (all P < 0.05) insulin-stimulated IRS-1 tyrosine phosphorylation (45%), IRS-1-associated p85 (72%), Akt1/2 serine phosphorylation (30%), and GSK3β serine phosphorylation (39%). Substantially smaller GSK3 inhibitor-mediated enhancements of insulin action on these insulin signaling factors were observed in obese epitrochlearis. These results indicate that selective GSK3 inhibition enhances insulin action in insulin-resistant skeletal muscle of the prediabetic obese Zucker rat, at least in part by relieving the deleterious effects of GSK3 action on post-IR insulin signaling. These effects of GSK3 inhibition on insulin action are greater in type I muscle than in type IIb muscle from these insulin-resistant animals.

Chronic rosiglitazone treatment restores AMPKα2 activity in insulin-resistant rat skeletal muscle

2006 ◽  
Vol 290 (2) ◽  
pp. E251-E257 ◽  
Author(s):  
Sarah J. Lessard ◽  
Zhi-Ping Chen ◽  
Matthew J. Watt ◽  
Michael Hashem ◽  
Julianne J. Reid ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zucker Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ampk Signaling ◽  
Palmitate Oxidation ◽  
Insulin Resistant ◽  
Obese Zucker Rats

Rosiglitazone (RSG) is an insulin-sensitizing thiazolidinedione (TZD) that exerts peroxisome proliferator-activated receptor-γ (PPARγ)-dependent and -independent effects. We tested the hypothesis that part of the insulin-sensitizing effect of RSG is mediated through the action of AMP-activated protein kinase (AMPK). First, we determined the effect of acute (30–60 min) incubation of L6 myotubes with RSG on AMPK regulation and palmitate oxidation. Compared with control (DMSO), 200 μM RSG increased ( P < 0.05) AMPKα1 activity and phosphorylation of AMPK (Thr172). In addition, acetyl-CoA carboxylase (Ser218) phosphorylation and palmitate oxidation were increased ( P < 0.05) in these cells. To investigate the effects of chronic RSG treatment on AMPK regulation in skeletal muscle in vivo, obese Zucker rats were randomly allocated into two experimental groups: control and RSG. Lean Zucker rats were treated with vehicle and acted as a control group for obese Zucker rats. Rats were dosed daily for 6 wk with either vehicle (0.5% carboxymethylcellulose, 100 μl/100 g body mass), or 3 mg/kg RSG. AMPKα1 activity was similar in muscle from lean and obese animals and was unaffected by RSG treatment. AMPKα2 activity was ∼25% lower in obese vs. lean animals ( P < 0.05) but was normalized to control values after RSG treatment. ACC phosphorylation was decreased with obesity ( P < 0.05) but restored to the level of lean controls with RSG treatment. Our data demonstrate that RSG restores AMPK signaling in skeletal muscle of insulin-resistant obese Zucker rats.

Altered basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from NIDDM patients compared with control subjects

Diabetologia ◽  
1996 ◽  
Vol 39 (10) ◽  
pp. 1208-1214 ◽  
Author(s):  
D. Worm ◽  
J. Vinten ◽  
P. Staehr ◽  
J. E. Henriksen ◽  
A. Handberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Phosphotyrosine Phosphatase ◽  
Control Subjects ◽  
Niddm Patients ◽  
Ptpase Activity

Insulin receptor kinase is hyperresponsive in adipocytes of young obese Zucker rats

1987 ◽  
Vol 252 (2) ◽  
pp. E273-E278 ◽  
Author(s):  
A. Debant ◽  
M. Guerre-Millo ◽  
Y. Le Marchand-Brustel ◽  
P. Freychet ◽  
M. Lavau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Insulin Action ◽  
Kinase Activity ◽  
Insulin Receptors ◽  
Zucker Rats ◽  
Receptor Kinase ◽  
Insulin Receptor Tyrosine Kinase ◽  
Obese Zucker Rats ◽  
Insulin Receptor Kinase

Thirty-day-old obese Zucker rats have hyperresponsive adipose tissue, whereas their skeletal muscle normally responds to insulin in vitro. To further substantiate the role of insulin receptor tyrosine kinase in insulin action, we have studied the kinase activity of receptors obtained from adipocytes and skeletal muscle of these young obese Zucker rats. Insulin receptors, partially purified by wheat germ agglutinin agarose chromatography from plasma membranes of isolated adipocytes or from skeletal muscles, were studied in a cell-free system for auto-phosphorylation and for their ability to phosphorylate a synthetic glutamate-tyrosine copolymer. For an identical amount of receptors, the insulin stimulatory action on its beta-subunit receptor phosphorylation was markedly augmented in preparations from hyperresponsive adipocytes of obese animals compared with lean rats. Basal phosphorylation of adipocyte insulin receptors was nearly identical in lean and obese animals. Similarly the capacity of adipocyte insulin receptors to catalyze the phosphorylation of the synthetic substrate in response to insulin was increased. By contrast, the kinase activity of insulin receptors prepared from normally insulin-responsive skeletal muscle was similar in preparations of lean and obese rats. These results show that a state of hyperresponsiveness to insulin is correlated with a parallel increase of insulin receptor kinase activity suggesting an important role for this activity in insulin action.

scholarly journals Peroxovanadates have full insulin-like effects on glycogen synthesis in normal and insulin-resistant skeletal muscle

1991 ◽  
Vol 276 (2) ◽  
pp. 289-292 ◽  
Author(s):  
B Leighton ◽  
G J S Cooper ◽  
C DaCosta ◽  
E A Foot
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Wistar Rats ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Lactate Formation ◽  
Total Glucose ◽  
Synergistic Increase

1. The insulin-like effects of orthovanadate (10 mM) and peroxides of vanadate (peroxovanadates, at 1 mM) on rates of lactate formation, glucose oxidation and glycogen synthesis were measured in incubated soleus-muscle preparations isolated from non-obese Wistar rats and lean (fa/?) or insulin-resistant obese Zucker (fa/fa) rats. 2. The stimulation of the rates of lactate formation and glucose oxidation by either orthovanadate or peroxovanadates was of similar magnitude to the stimulation by a maximally effective concentration of insulin (1000 microunits/ml). 3. Peroxovanadates, but not orthovanadate, maximally stimulated the rate of glycogen synthesis in incubated soleus muscles isolated from Wistar rats. 4. When soleus-muscle preparations were incubated in the presence of both insulin (1000 microunits/ml) and peroxovanadates (1 mM), this did not result in a synergistic increase in the rate of total glucose utilization as compared with either agent alone. 5. Soleus muscles isolated from obese (fa/fa) Zucker rats exhibited a decrease in response to a physiologically relevant concentration of insulin (100 microunits/ml). Peroxovanadates, at 1 mM, maximally stimulated the rate of glycogen synthesis in soleus muscles isolated from obese (fa/fa) Zucker rats. 6. The findings indicate that peroxovanadates are useful and important agents for investigating the mechanism of action of insulin in skeletal muscle.

scholarly journals Insulin-induced translocation of GLUT 4 in skeletal muscle of insulin-resistant Zucker rats

Diabetologia ◽  
1994 ◽  
Vol 37 (1) ◽  
pp. 3-9 ◽  
Author(s):  
P. Galante ◽  
E. Maerker ◽  
R. Scholz ◽  
K. Rett ◽  
L. Herberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Glut 4

Increased Oxidative and Delayed Glycogenolytic ATP Synthesis in Exercising Skeletal Muscle of Obese (Insulin-Resistant) Zucker Rats

1996 ◽  
Vol 91 (6) ◽  
pp. 691-702 ◽  
Author(s):  
A. L. Sanderson ◽  
G. J. Kemp ◽  
C. H. Thompson ◽  
G. K. Radda
Keyword(s):  
Skeletal Muscle ◽  
Water Content ◽  
Atp Synthesis ◽  
Intracellular Water ◽  
Zucker Rats ◽  
Resonance Spectroscopy ◽  
Metabolic Efficiency ◽  
Marker Enzyme ◽  
Insulin Resistant ◽  
Kinetics Of

1. To examine metabolic correlates of insulin resistance in skeletal muscle, we used 31P magnetic resonance spectroscopy to study glycogenolytic and oxidative ATP synthesis in leg muscle of lean and obese Zucker rats in vivo during 6 min sciatic nerve stimulation at 2 Hz. 2. The water content of resting muscle was reduced by 21 ± 7% in obese (insulin-resistant) animals compared with lean animals, whereas the lipid content was increased by 140 ± 70%. These results suggest that intracellular water content was reduced by 17% in obese animals. 3. During exercise, although twitch tensions were not significantly different in the two groups, rates of total ATP synthesis (expressed per litre of intracellular water) were 48 ± 20% higher in obese animals, suggesting a 50 ± 8% reduction in intrinsic ‘metabolic efficiency’. Changes in phosphocreatine and ADP concentration were significantly greater in obese animals than in lean animals, whereas changes in intracellular pH did not differ. 4. These results imply that oxidative ATP synthesis during exercise is activated earlier in obese animals than in lean animals. This difference was not fully accounted for by the greater increase in the concentration of the mitochondrial activating signal ADP. Neither the post-exercise recovery kinetics of phosphocreatine nor the muscle content of the mitochondrial marker enzyme citrate synthase was significantly different in the two groups. The increased oxidative ATP synthesis in exercise must therefore be due to altered kinetics of mitochondrial activation by signals other than ADP. 5. Thus, the insulin-resistant muscle of obese animals may compensate for its decreased efficiency (and consequent increased need for ATP) by increased reliance on oxidative ATP synthesis.

Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle

2002 ◽  
Vol 92 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Vitoon Saengsirisuwan ◽  
Felipe R. Perez ◽  
Tyson R. Kinnick ◽  
Erik J. Henriksen
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Exercise Training ◽  
Glucose Transport ◽  
Insulin Action ◽  
Treadmill Running ◽  
Protein Carbonyls ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Insulin Resistant

We have recently demonstrated (Saengsirisuwan V, Kinnick TR, Schmit MB, and Henriksen EJ, J Appl Physiol 91: 145–153, 2001) that exercise training (ET) and the antioxidant R-(+)-α-lipoic acid ( R-ALA) interact in an additive fashion to improve insulin action in insulin-resistant obese Zucker ( fa/fa) rats. The purpose of the present study was to assess the interactions of ET and R-ALA on insulin action and oxidative stress in a model of normal insulin sensitivity, the lean Zucker ( fa/−) rat. For 6 wk, 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. ET alone or in combination with R-ALA significantly increased ( P < 0.05) peak oxygen consumption (28–31%) and maximum run time (52–63%). During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose response (17–36%) at 15 min relative to R-ALA alone and of the insulin response (19–36%) at 15 min compared with sedentary controls. Insulin-mediated glucose transport activity was increased by ET alone in isolated epitrochlearis (30%) and soleus (50%) muscles, and this was associated with increased GLUT-4 protein levels. Insulin action was not improved by R-ALA alone, and ET-associated improvements in these variables were not further enhanced with combined ET and R-ALA. Although ET and R-ALA caused reductions in soleus protein carbonyls (an index of oxidative stress), these alterations were not significantly correlated with insulin-mediated soleus glucose transport. These results indicate that the beneficial interactive effects of ET and R-ALA on skeletal muscle insulin action observed previously in insulin-resistant obese Zucker rats are not apparent in insulin-sensitive lean Zucker rats.

Sign in / Sign up

Export Citation Format

Share Document