scholarly journals The Effects of Altitude Training on the AMPK-Related Glucose Transport Pathway in the Red Skeletal Muscle of Both Lean and Obese Zucker Rats

2011 ◽  
Vol 12 (4) ◽  
pp. 371-378 ◽  
Author(s):  
Yu-Ching Chen ◽  
Shin-Da Lee ◽  
Low-Tone Ho ◽  
Cha-Hua Kuo
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Zucker Rats ◽  
Altitude Training ◽  
Transport Pathway ◽  
Obese Zucker Rats

scholarly journals Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

2012 ◽  
Vol 302 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
Elizabeth M. Marchionne ◽  
Maggie K. Diamond-Stanic ◽  
Mujalin Prasonnarong ◽  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Renin Inhibition

We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker ( fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser473 phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance.

scholarly journals Contractile activity restores insulin responsiveness in skeletal muscle of obese Zucker rats

1993 ◽  
Vol 289 (2) ◽  
pp. 423-426 ◽  
Author(s):  
P L Dolan ◽  
E B Tapscott ◽  
P J Dorton ◽  
G L Dohm
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Contractile Activity ◽  
Clinical Importance ◽  
Zucker Rats ◽  
Insulin Resistant ◽  
Significant Difference ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Insulin Responsiveness

Both insulin and contraction stimulate glucose transport in skeletal muscle. Insulin-stimulated glucose transport is decreased in obese humans and rats. The aims of this study were (1) to determine if contraction-stimulated glucose transport was also compromised in skeletal muscle of genetically obese insulin-resistant Zucker rats, and (2) to determine whether the additive effects of insulin and contraction previously observed in muscle from lean subjects were evident in muscle from the obese animals. To measure glucose transport, hindlimbs from lean and obese Zucker rats were perfused under basal, insulin-stimulated (0.1 microM), contraction-stimulated (electrical stimulation of the sciatic nerve) and combined insulin-(+)contraction-stimulated conditions. One hindlimb was stimulated to contract while the contralateral leg served as an unstimulated control. 2-Deoxyglucose transport rates were measured in the white gastrocnemius, red gastrocnemius and extensor digitorum longus muscles. As expected, the insulin-stimulated glucose transport rate in each of the three muscles was significantly slower (P < 0.05) in obese rats when compared with lean animals. When expressed as fold stimulation over basal, there was no significant difference in contraction-induced muscle glucose transport rates between lean and obese animals. Insulin-(+)contraction-stimulation was additive in skeletal muscle of lean animals, but synergistic in skeletal muscle of obese animals. Prior contraction increased insulin responsiveness of glucose transport 2-5-fold in the obese rats, but had no effect on insulin responsiveness in the lean controls. This contraction-induced improvement in insulin responsiveness could be of clinical importance to obese subjects as a way to improve insulin-stimulated glucose uptake in resistant skeletal muscle.

scholarly journals Glucose metabolism in perfused skeletal muscle. Demonstration of insulin resistance in the obese Zucker rat

1979 ◽  
Vol 178 (3) ◽  
pp. 733-741 ◽  
Author(s):  
F W Kemmer ◽  
M Berger ◽  
L Herberg ◽  
F A Gries ◽  
A Wirdeier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Muscle Cell ◽  
Inhibitory Effect ◽  
Zucker Rats ◽  
Control Group ◽  
Lactate Oxidation ◽  
Obese Zucker Rats

1. The effect of insulin (0.5, 10 and 50 munits/ml of perfusate) on glucose uptake and disposal in skeletal muscle was studied in the isolated perfused hindquarter of obese (fa/fa) and lean (Fa/Fa) Zucker rats and Osborne-Mendel rats. 2. A concentration of 0.5 munit of insulin/ml induced a significant increase in glucose uptake (approx. 2.5 mumol/min per 30 g of muscle) in lean Zucker rats and in Osborne-Mendel rats, and 10 munits of insulin/ml caused a further increase to approx. 6 mumol/min per 30 g of muscle; but 50 munits of insulin/ml had no additional stimulatory effect. In contrast, in obese Zucker rats only 10 and 50 munits of insulin/ml had a stimulatory effect on glucose uptake, the magnitude of which was decreased by 50-70% when compared with either lean control group. Since under no experimental condition tested was an accumulation of free glucose in muscle-cell water observed, the data suggest an impairment of insulin-stimulated glucose transport across the muscle-cell membrane in obese Zucker rats. 3. The intracellular disposal of glucose in skeletal muscle of obese Zucker rats was also insulin-insensitive: even at insulin concentrations that clearly stimulated glucose uptake, no effect of insulin on lactate oxidation (nor an inhibitory effect on alanine release) was observed; [14C]glucose incorporation into skeletal-muscle lipids was stimulated by 50 munits of insulin/ml, but the rate was still only 10% of that observed in lean Zucker rats. 4. The data indicate that the skeletal muscle of obese Zucker rats is insulin-resistant with respect to both glucose-transport mechanisms and intracellular pathways of glucose metabolism, such as lactate oxidation. The excessive degree of insulin-insensitivity in skeletal muscle of obese Zucker rats may represent a causal factor in the development of the glucose intolerance in this species.

Stimulation by α-Lipoic acid of glucose transport activity in skeletal muscle of lean and obese zucker rats

Life Sciences ◽  
1997 ◽  
Vol 61 (8) ◽  
pp. 805-812 ◽  
Author(s):  
Erik J. Henriksen ◽  
Stephan Jacob ◽  
Ryan S. Streeper ◽  
Donovan L. Fogt ◽  
Jason Y. Hokama ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Lipoic Acid ◽  
Zucker Rats ◽  
Transport Activity ◽  
Obese Zucker Rats

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.

Chronic selective glycogen synthase kinase-3 inhibition enhances glucose disposal and muscle insulin action in prediabetic obese Zucker rats

2006 ◽  
Vol 291 (2) ◽  
pp. E207-E213 ◽  
Author(s):  
Betsy B. Dokken ◽  
Erik J. Henriksen
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Glycogen Synthase ◽  
Whole Body ◽  
Zucker Rats ◽  
Oral Glucose ◽  
Insulin Resistant ◽  
Obese Zucker Rats

Increasing evidence supports a negative role of glycogen synthase kinase-3 (GSK-3) in regulation of skeletal muscle glucose transport. We assessed the effects of chronic treatment of insulin-resistant, prediabetic obese Zucker ( fa/ fa) rats with a highly selective GSK-3 inhibitor (CT118637) on glucose tolerance, whole body insulin sensitivity, plasma lipids, skeletal muscle insulin signaling, and in vitro skeletal muscle glucose transport activity. Obese Zucker rats were treated with either vehicle or CT118637 (30 mg/kg body wt) twice per day for 10 days. Fasting plasma insulin and free fatty acid levels were reduced by 14 and 23% ( P < 0.05), respectively, in GSK-3 inhibitor-treated animals compared with vehicle-treated controls. The glucose response during an oral glucose tolerance test was reduced by 18% ( P < 0.05), and whole body insulin sensitivity was increased by 28% ( P < 0.05). In vivo insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (50%) and IRS-1-associated phosphatidylinositol-3′ kinase (79%) relative to fasting plasma insulin levels were significantly elevated ( P < 0.05) in plantaris muscles of GSK-3 inhibitor-treated animals. Whereas basal glucose transport in isolated soleus and epitrochlearis muscles was unaffected by chronic GSK-3 treatments, insulin stimulation of glucose transport above basal was significantly enhanced (32–60%, P < 0.05). In summary, chronic treatment of insulin-resistant, prediabetic obese Zucker rats with a specific GSK-3 inhibitor enhances oral glucose tolerance and whole body insulin sensitivity and is associated with an amelioration of dyslipidemia and an improvement in IRS-1-dependent insulin signaling in skeletal muscle. These results provide further evidence that selective targeting of GSK-3 in muscle may be an effective intervention for the treatment of obesity-associated insulin resistance.

Effects of a unique conjugate of α-lipoic acid and γ-linolenic acid on insulin action in obese Zucker rats

2000 ◽  
Vol 278 (2) ◽  
pp. R453-R459 ◽  
Author(s):  
J. Anthony Peth ◽  
Tyson R. Kinnick ◽  
Erik B. Youngblood ◽  
Hans J. Tritschler ◽  
Erik J. Henriksen
Keyword(s):  
Fatty Acid ◽  
Essential Fatty Acid ◽  
Glucose Transport ◽  
Lipoic Acid ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Additive Effects ◽  
Insulin Resistant ◽  
Obese Zucker Rats

The purpose of this study was to assess the individual and interactive effects of the antioxidant α-lipoic acid (LPA) and the n-6 essential fatty acid γ-linolenic acid (GLA) on insulin action in insulin-resistant obese Zucker rats. LPA, GLA, and a unique conjugate consisting of equimolar parts of LPA and GLA (LPA-GLA) were administered for 14 days at 10, 30, or 50 mg ⋅ kg body wt− 1 ⋅ day− 1. Whereas LPA was without effect at 10 mg/kg, at 30 and 50 mg/kg it elicited 23% reductions ( P < 0.05) in the glucose-insulin index (the product of glucose and insulin areas under the curve during an oral glucose tolerance test and an index of peripheral insulin action) that were associated with significant increases in insulin-mediated (2 mU/ml) glucose transport activity in isolated epitrochlearis (63–65%) and soleus (33–41%) muscles. GLA at 10 and 30 mg/kg caused 21–25% reductions in the glucose-insulin index and 23–35% improvements in insulin-mediated glucose transport in epitrochlearis muscle. The beneficial effects of GLA disappeared at 50 mg/kg. At 10 and 30 mg/kg, the LPA-GLA conjugate elicited 29 and 38% reductions in the glucose-insulin index. These LPA-GLA-induced improvements in whole body insulin action were accompanied by 28–63 and 38–57% increases in insulin-mediated glucose transport in epitrochlearis and soleus muscles and resulted from the additive effects of LPA and GLA. At 50 mg/kg, the metabolic improvements due to LPA-GLA were substantially reduced. In summary, these results indicate that the conjugate of the antioxidant LPA and the n-6 essential fatty acid GLA elicits significant dose-dependent improvements in whole body and skeletal muscle insulin action on glucose disposal in insulin-resistant obese Zucker rats. Moreover, these actions of LPA-GLA are due to the additive effects of its individual components.

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