Skeletal muscle glucose transport in obese Zucker rats after exercise training

1989 ◽  
Vol 66 (6) ◽  
pp. 2635-2641 ◽  
Author(s):  
J. L. Ivy ◽  
J. T. Brozinick ◽  
C. E. Torgan ◽  
G. M. Kastello
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
Transport Process ◽  
Fiber Type ◽  
Zucker Rat ◽  
Muscle Insulin Resistance ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Muscle Glucose Transport ◽  
Fast Twitch

Exercise training has been found to reduce the muscle insulin resistance of the obese Zucker rat (fa/fa). The purpose of the present study was to determine whether this reduction in muscle insulin resistance was associated with an improvement in the glucose transport process and if it was fiber-type specific. Rats were randomly assigned to a sedentary or training group. Training consisted of treadmill running at 18 m/min up an 8% grade, 1.5 h/day, 5 days/wk, for 6–8 wk. The rate of muscle glucose transport was assessed in the absence of insulin and in the presence of a physiological (0.15 mU/ml), a submaximal (1.50 mU/ml), and a maximal (15.0 mU/ml) insulin concentration by determining the rate of 3-O-methyl-D-glucose (3-OMG) accumulation during hindlimb perfusion. The average 3-OMG transport rate of the red gastrocnemii (fast-twitch oxidative-glycolytic fibers) was significantly higher in the trained compared with the sedentary obese rats in the absence of insulin and in the presence of the three insulin concentrations. Significant improvements in 3-OMG transport were also observed in the plantarii (mixed fibers) of trained obese rats in the presence of 0, 0.15, and 15.0 mU/ml insulin. Training appeared to have little effect on the insulin-stimulated 3-OMG transport of the soleus (slow-twitch oxidative fibers) or white gastrocnemius (fast-twitch glycolytic fibers). The results suggest that the improvement in the muscle insulin resistance of the obese Zucker rat after moderate endurance training was associated with an improvement in the glucose transport process but that it was fiber-type specific.

Glucose transport: locus of muscle insulin resistance in obese Zucker rats

1988 ◽  
Vol 255 (3) ◽  
pp. E374-E382 ◽  
Author(s):  
W. M. Sherman ◽  
A. L. Katz ◽  
C. L. Cutler ◽  
R. T. Withers ◽  
J. L. Ivy
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glycogen Synthase ◽  
Fiber Type ◽  
Zucker Rats ◽  
Muscle Insulin Resistance ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Fast Twitch

The purposes of this study were to determine whether the muscle insulin resistance of the obese rat is due to a defect in the glucose transport process and whether the insulin resistance is fiber-type specific. The hindlimbs of fasted, 14-wk-old obese (fa/fa) and lean (fa/?) Zucker rats were perfused with perfusate containing 8 mM glucose and no insulin or 8 mM glucose and either a physiological (0.15 mU/ml), a submaximal (1.50 mU/ml), or a maximal (15.0 mU/ml) insulin concentration. Glucose uptake was determined after which the initial rate of glucose transport was determined using 3-O-methyl-D-glucose (3-OMG). Glucose uptake of the obese rats was depressed by 40, 33, 42, and 47% in the absence of insulin and in the presence of the physiological, submaximal, and maximal insulin concentrations, respectively, when compared with lean littermates. Glucose transport in the absence and in the presence of the three insulin concentrations was significantly lower in the soleus (slow-twitch, oxidative fibers), red quadriceps (fast-twitch, oxidative, glycolytic fibers), and gastrocnemius (mixed fibers) of the obese rats when compared with lean rats. Glucose transport in the white quadriceps (fast-twitch, glycolytic fibers) was significantly lower in the obese rats in the absence of insulin and in the presence of the submaximal and maximal insulin concentrations. The glycogen concentration and the activity of hexokinase were the same and the glycogen synthase activity was higher in the muscles for the obese rats when compared to lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats

1992 ◽  
Vol 263 (5) ◽  
pp. E1015-E1020 ◽  
Author(s):  
E. A. Banks ◽  
J. T. Brozinick ◽  
B. B. Yaspelkis ◽  
H. Y. Kang ◽  
J. L. Ivy
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Glucose Transporter ◽  
Citrate Synthase ◽  
Fiber Type ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Glut 4 ◽  
Obese Zucker Rat ◽  
Fast Twitch

The effects of high (HI)- and low (LI)-intensity exercise training were examined on insulin-stimulated 3-O-methyl-d-glucose (3-MG) transport and concentration of insulin-regulatable glucose transporter protein (GLUT-4) in the red (fast-twitch oxidative) and white (fast-twitch glycolytic) quadriceps of the obese Zucker rat. Sedentary obese (SED) and lean (LN) Zucker rats were used as controls. 3-MG transport was determined during hindlimb perfusion in the presence of 8 mM 3-MG, 2 mM mannitol, 0.3 mM pyruvate, and 0.5 mU/ml insulin. HI and LI rats displayed greater rates of red quadriceps 3-MG transport and GLUT-4 concentrations than SED rats. No significant differences in rates of 3-MG transport or GLUT-4 concentrations were observed in the red quadriceps of HI and LI rats. There were no differences found in the rates of 3-MG transport in the white quadriceps of HI, LI, and SED rats although the difference between the HI and SED rats approached significance (P < 0.07). The GLUT-4 concentration and citrate synthase activity of HI rats were significantly greater than SED rats. The 3-MG transport rates of LN rats were twofold greater than SED rats regardless of fiber type, but a difference in GLUT-4 content between the LN and SED rats was observed only in the white quadriceps. GLUT-4 content of the obese rats was significantly correlated with citrate synthase activity (r = 0.93) and 3-MG transport (r = 0.82). The results suggest that the improvement in muscle insulin resistance of the obese Zucker rat after exercise training is due in part to an increased GLUT-4 concentration, which is related with the degree to which the muscle is trained. glucose transporter; insulin; insulin resistance; diabetes, muscle fiber type Submitted on May 21, 1992 Accepted on July 31, 1992

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.

Exercise and diet reduce muscle insulin resistance in obese Zucker rat

1986 ◽  
Vol 251 (3) ◽  
pp. E299-E305 ◽  
Author(s):  
J. L. Ivy ◽  
W. M. Sherman ◽  
C. L. Cutler ◽  
A. L. Katz
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
High Carbohydrate Diet ◽  
Carbohydrate Diet ◽  
Muscle Insulin Resistance ◽  
High Carbohydrate ◽  
Obese Zucker Rat ◽  
Obese Rats

Two treatments that increase skeletal muscle insulin action are exercise training and high-carbohydrate diet. The purpose of the present study was to determine whether exercise training and a diet high in carbohydrates could function synergistically to reduce the muscle insulin resistance in the obese Zucker rat. Obese rats 4 wk of age were randomly assigned to an exercise or sedentary group. Each group was subdivided by diet with one-half of the rats fed a high-carbohydrate diet and one-half fed a high-fat diet. Lean Zucker rats fed the high-fat diet were used as controls. Muscle insulin resistance was assessed during hindlimb perfusion with a submaximally stimulating concentration of insulin. Exercise training and the high-carbohydrate diet increased the rate of muscle glucose uptake in the obese rat by 46 and 53%, respectively. More importantly, the combined effect of exercise training and high-carbohydrate diet was greater than the sum of their individual effects. Glycogen synthesis paralleled glucose uptake and was the major pathway for intracellular glucose disposal. Muscle glucose uptake for exercise-trained, high-carbohydrate fed obese rats was comparable with that of lean controls. It is concluded that exercise training and the high-carbohydrate diet functioned synergistically to reduce the muscle insulin resistance in the obese rat.

scholarly journals Changes in individual rates of pancreatic enzyme and isoenzyme biosynthesis in the obese Zucker rat

1987 ◽  
Vol 248 (3) ◽  
pp. 771-777 ◽  
Author(s):  
E R Trimble ◽  
U Rausch ◽  
H F Kern
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Pancreatic Enzyme ◽  
Acinar Cells ◽  
Enzyme Synthesis ◽  
Secretory Response ◽  
Zucker Rat ◽  
Enzyme Content ◽  
Obese Zucker Rat ◽  
Obese Rats

Both alterations of enzyme content and a markedly decreased secretory response to selected physiological stimuli have been demonstrated previously in the pancreas of the obese Zucker rat. The purpose of the present investigation was to determine the degree to which alterations of enzyme content could be attributed to changes in enzyme biosynthesis. Amylase content of obese rats was decreased by 50%, whereas lipase and trypsinogens were significantly increased. However, the decrease in amylase content was less than might have been predicted from the rate of amylase biosynthesis (80% decrease), and the increases in content of trypsinogen(s) and lipase were greater than would have been predicted from alterations in the absolute rates of biosynthesis. In view of the rapid turnover of pancreatic enzymes under normal conditions, it seems probable that a markedly decreased secretory response to various stimuli leads to an increased content of some enzymes in the pancreas of the obese rat. Ciglitazone treatment, which decreases insulin resistance in obese animals and leads to normalization of glucose metabolism in their pancreatic tissue, restored the enzyme-synthesis rates towards normal, showing that the abnormalities of enzyme synthesis were linked to the insulin resistance rather than to the obese genotype itself. Lipid inclusion bodies were found in acinar cells of obese rats. These bodies have previously been described in acinar cells of starved animals, which, in common with the acinar tissue of the obese Zucker rat, have decreased glucose metabolism.

scholarly journals Changes in content and secretion of pancreatic enzymes in the obese Zucker rat

1984 ◽  
Vol 219 (1) ◽  
pp. 333-336 ◽  
Author(s):  
R Bruzzone ◽  
E R Trimble ◽  
A Gjinovci ◽  
A E Renold
Keyword(s):  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Digestive Enzymes ◽  
Enzyme Secretion ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Old Rats ◽  
Obese Zucker Rats

The contents of three major digestive enzymes (amylase, lipase and chymotrypsinogen) were measured in the obese Zucker rat. Only minimal changes were found in 7-week-old rats, but in adult obese rats (14-16 weeks) the amylase content was decreased by 50%, whereas the lipase and chymotrypsinogen contents were increased by 45% and 20%, respectively, compared with lean controls. Abnormalities of enzyme secretion were also found. Since the changes observed in enzyme proportions in adult obese Zucker rats are qualitatively similar to those observed in insulinopenic diabetes and other states associated with decreased glucose metabolism, it is speculated that the abnormalities found in the obese Zucker rat may be due to decreased glucose metabolism in the exocrine tissue consequent to insulin resistance.

Exercise training reverses insulin resistance in muscle by enhanced recruitment of GLUT-4 to the cell surface

1997 ◽  
Vol 272 (5) ◽  
pp. E864-E869 ◽  
Author(s):  
G. J. Etgen ◽  
J. Jensen ◽  
C. M. Wilson ◽  
D. G. Hunt ◽  
S. W. Cushman ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cell Surface ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Zucker Rat ◽  
Transport Activity ◽  
Glut 4 ◽  
Obese Zucker Rat ◽  
Slow Twitch ◽  
Fast Twitch

The effects of exercise training on cell surface GLUT-4 in skeletal muscle of the obese (fa/fa) Zucker rat were investigated using the impermeant glucose transporter photoaffinity reagent 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1,3-bis- (D-mannos-4-yloxy)-2-propylamine (ATB-BMPA). In the absence of insulin, 3-O-methyl-D-glucose transport activity was no different in either fast-twitch (epitrochlearis) or slow-twitch (soleus) muscles of trained and sedentary obese rats. Likewise, basal ATB-BMPA-labeled GLUT-4 was not altered in these muscles with training. In contrast, the trained group exhibited significantly greater insulin-stimulated (2 mU/ml) glucose transport activity in epitrochlearis muscles than the sedentary group (0.53 +/- 0.03 vs. 0.18 +/- 0.03 mumol.g-1 x 10 min-1 for trained and sedentary, respectively), which was paralleled by a significant enhancement of insulin-stimulated cell surface GLUT-4 (5.33 +/- 0.20 vs. 1.57 +/- 0.14 disintegrations.min-1.mg-1 for trained and sedentary, respectively). Exercise training, however, did not alter insulin-stimulated glucose transport activity or cell surface GLUT-4 in soleus muscles. Finally, exercise training did not alter the ability of muscle contraction to elevate glucose transport activity or cell surface GLUT-4 in either epitrochlearis or soleus muscles of the obese rat. These results indicate that training improves insulin-stimulated glucose transport in muscle of the obese Zucker rat by increasing GLUT-4 content and by altering the normal intracellular distribution of these transporters such that they are now capable of migrating to the cell surface in response to the insulin stimulus.

scholarly journals Insulin resistance is accompanied by impairment of amylase-gene expression in the exocrine pancreas of the obese Zucker rat

1986 ◽  
Vol 237 (3) ◽  
pp. 807-812 ◽  
Author(s):  
E R Trimble ◽  
R Bruzzone ◽  
D Belin
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Glucose Metabolism ◽  
Pancreatic Amylase ◽  
Zucker Rat ◽  
Amylase Gene ◽  
Plasma Insulin Concentration ◽  
Pancreatic Acini ◽  
Obese Zucker Rat ◽  
Obese Rats

Insulin plays a major role in the control of pancreatic amylase biosynthesis. In this study we determined glucose metabolism by pancreatic acini as well as the pancreatic content of both amylase protein and amylase mRNA during development of insulin resistance in the obese Zucker rat. At age 4 weeks there were no abnormalities detected in the above parameters, although the obese animals were already hyperinsulinaemic. At 6 weeks glucose metabolism was decreased by 50% in acini from obese rats, whereas pancreatic amylase-gene expression was only slightly impaired. At 22 weeks glucose metabolism was decreased by 50%, amylase content by 55% and amylase mRNA by 60% in acinar tissue of obese rats. As expected, hyperinsulinaemia increased markedly with age. Thus development of severe insulin resistance was associated with impairment of amylase-gene expression. To decrease insulin resistance, one group of adult obese rats was treated with Ciglitazone for 4 weeks. A lowered plasma insulin concentration without alteration of food intake was taken as evidence of decreased insulin resistance. This was associated with normalization of glucose metabolism and a marked increase of both amylase content of pancreatic tissue and amylase mRNA. In conclusion, both the increase of insulin resistance with age and its partial reversal by Ciglitazone treatment appear to modulate pancreatic amylase-gene expression in the obese Zucker rat.

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