Glucose uptake and GLUT-4 protein distribution in skeletal muscle of the obese Zucker rat

1994 ◽  
Vol 267 (1) ◽  
pp. R236-R243 ◽  
Author(s):  
J. T. Brozinick ◽  
G. J. Etgen ◽  
B. B. Yaspelkis ◽  
J. L. Ivy
Keyword(s):  
Plasma Membrane ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Protein Translocation ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Protein Distribution ◽  
Glut 4 ◽  
Obese Zucker Rat ◽  
Obese Rats

The rates of muscle glucose uptake of lean and obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin), in the presence of a maximally stimulating concentration of insulin (10 mU/ml), and after muscle contraction elicited by electrical stimulation of the sciatic nerve. After perfusion, plasma and microsomal membranes were isolated from selected hindlimb muscles for determination of GLUT-4 protein distribution. Under basal conditions, rates of glucose uptake were similar for lean and obese rats despite plasma membranes from lean rats containing 82% more GLUT-4 protein than obese rats. Insulin stimulation resulted in significant increases in plasma membrane GLUT-4 protein concentration in lean but not obese rats. Glucose uptake of lean rats (35.3 +/- 4.7 mumol.h-1.g-1) in the presence of insulin was approximately fourfold greater than that of obese rats (8.8 +/- 1.3 mumol.h-1.g-1), but this difference in glucose uptake could not be completely accounted for by the difference in plasma membrane GLUT-4 protein concentration. Stimulation by contraction resulted in significant increases in plasma membrane GLUT-4 protein concentration in both lean and obese rats and similar rates of glucose uptake. These results suggest that the muscle insulin resistance of the obese Zucker rat is due to 1) a reduced plasma membrane GLUT-4 protein concentration, which results in part from an impairment in the insulin-stimulated GLUT-4 protein translocation process, and 2) a defect in the insulin-stimulated activation of this protein. However, contraction-stimulated glucose uptake, GLUT-4 protein translocation, and activation are normal in the obese Zucker rat.

scholarly journals The effects of muscle contraction and insulin on glucose-transporter translocation in rat skeletal muscle

1994 ◽  
Vol 297 (3) ◽  
pp. 539-545 ◽  
Author(s):  
J T Brozinick ◽  
G J Etgen ◽  
B B Yaspelkis ◽  
J L Ivy
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Protein Distribution ◽  
Sprague Dawley ◽  
Glut 4

The effect of electrically induced muscle contraction, insulin (10 m-units/ml) and electrically-induced muscle contraction in the presence of insulin on insulin-regulatable glucose-transporter (GLUT-4) protein distribution was studied in female Sprague-Dawley rats during hindlimb perfusion. Plasma-membrane cytochalasin B binding increased approximately 2-fold, whereas GLUT-4 protein concentration increased approximately 1.5-fold above control with contractions, insulin, or insulin + contraction. Microsomal-membrane cytochalasin B binding and GLUT-4 protein concentration decreased by approx. 30% with insulin or insulin + contraction, but did not significantly decrease with contraction alone. The rate of muscle glucose uptake was assessed by determining the rate of 2-deoxy[3H]glucose accumulation in the soleus, plantaris, and red and white portions of the gastrocnemius. Both contraction and insulin increased glucose uptake significantly and to the same degree in the muscles examined. Insulin + contraction increased glucose uptake above that of insulin or contraction alone, but this effect was only statistically significant in the soleus, plantaris and white gastrocnemius. The combined effects of insulin + contraction of glucose uptake were not fully additive in any of the muscles investigated. These results suggest that (1) insulin and muscle contraction are mobilizing two separate pools of GLUT-4 protein, and (2) the increase in skeletal-muscle glucose uptake due to insulin + contraction is not due to an increase in plasma-membrane GLUT-4 protein concentration above that observed for insulin or contraction alone.

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.

Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats

1993 ◽  
Vol 265 (3) ◽  
pp. E419-E427 ◽  
Author(s):  
J. T. Brozinick ◽  
G. J. Etgen ◽  
B. B. Yaspelkis ◽  
H. Y. Kang ◽  
J. L. Ivy
Keyword(s):  
Plasma Membrane ◽  
Exercise Training ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Protein Concentration ◽  
Citrate Synthase ◽  
Zucker Rats ◽  
Glut 4 ◽  
Basal Plasma ◽  
Obese Zucker Rats

The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin-stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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 Gene expression of lipid storage-related enzymes in adipose tissue of the genetically obese Zucker rat. Co-ordinated increase in transcriptional activity and potentiation by hyperinsulinaemia

1992 ◽  
Vol 281 (3) ◽  
pp. 607-611 ◽  
Author(s):  
I Dugail ◽  
A Quignard-Boulangé ◽  
X Le Liepvre ◽  
B Ardouin ◽  
M Lavau
Keyword(s):  
Adipose Tissue ◽  
Mrna Level ◽  
Lipid Storage ◽  
Zucker Rats ◽  
Transcriptional Level ◽  
Transcription Rate ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats

The genetically obese Zucker rat displays excessive fat storage capacity which is due to a tissue-specific increase in the activities of a number of lipid storage-related enzymes in adipose tissue. The aim of this study was to investigate the molecular mechanism responsible for this phenomenon. Lean (Fa/fa) and obese (fa/fa) Zucker rats were studied during the early stages of adipose tissue overdevelopment, both before (at 16 days of age) and after (at 30 days of age) the emergence of hyperinsulinaemia, in order to delineate the effects of the fatty genotype independently of those of hyperinsulinaemia. Lipoprotein lipase (LPL), glycerophosphate dehydrogenase (GPDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and malic enzyme (ME) mRNA levels in the adipose tissue of lean and obese rats were assessed by Northern blot analysis, and the relative transcription rates of the corresponding genes were compared in the two genotypes by a nuclear run-on assay. In normoinsulinaemic 16-day-old pre-obese rats, mRNA levels were increased over control values (LPL, 5-fold; ME, 2-fold; GAPDH, 3-fold), in close correlation with genotype-mediated differences in enzyme activities. Stimulation of the transcription rates of the ME and GAPDH genes was observed in obese rats, which could fully account for differences in steady-state mRNA levels. At this age, GPDH activity, mRNA level and transcription rate were similar in the two genotypes. In hyperinsulinaemic 30-day-old obese rats, a 6-7-fold increase in both mRNA and the transcription rate of GPDH emerged, together with an amplification of the genotype-mediated differences observed in younger animals (GAPDH, 6-fold; ME, 7.9-fold; LPL, 10-fold). These results demonstrate that the obese genotype exerts a co-ordinated control on the expression of these genes in adipose tissue, mainly at the transcriptional level. This genotype effect is greatly amplified by the development of hyperinsulinaemia.

scholarly journals Adipsin mRNA amounts are not decreased in the genetically obese Zucker rat

1989 ◽  
Vol 257 (3) ◽  
pp. 917-919 ◽  
Author(s):  
I Dugail ◽  
X Le Liepvre ◽  
A Quignard-Boulangé ◽  
J Pairault ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Mice ◽  
High Fat ◽  
Adult Rats ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats

Adipsin gene expression as assessed by mRNA amounts was examined in adipose tissue of genetically obese rats at the onset (16 days of age) or at later stages (30 and 60 days of age) of obesity. Amounts of mRNA were equivalent in obese and lean rats at 16 days of age. In adult rats, we observed a 2-fold decrease in adipsin mRNA in the obese rats compared with control lean rats, which was abolished by weaning the animals on a high-fat diet. Our data show that, in sharp contrast with genetically obese mice, adipsin mRNA is not suppressed in genetically obese Zucker rats.

Interaction of exercise training and clenbuterol on GLUT-4 protein in muscle of obese Zucker rats

1996 ◽  
Vol 271 (5) ◽  
pp. E847-E854 ◽  
Author(s):  
C. H. Kuo ◽  
Z. Ding ◽  
J. L. Ivy
Keyword(s):  
Exercise Training ◽  
Adrenergic Receptors ◽  
Protein Concentration ◽  
Chronic Administration ◽  
Zucker Rats ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Glut 4 ◽  
Obese Zucker Rat ◽  
Obese Zucker Rats

Chronic administration of clenbuterol, a beta 2-adrenergic agonist, attenuates the exercise training-induced improvement in muscle insulin resistance of the obese Zucker rat. The present study was conducted to determine whether clenbuterol also attenuates the increase in muscle GLUT-4 protein that occurs with exercise training and whether the action of clenbuterol is related to its ability to downregulate the beta-adrenergic receptors. Female obese Zucker rats were randomly assigned to one of the following four groups: control (CON, n = 7), clenbuterol (CL, n = 8), exercise training (TR, n = 8), and clenbuterol with exercise training (CL+TR, n = 8). Rats assigned to the training groups were run on a rodent motor-driven treadmill for 6-7 wk. Rats receiving clenbuterol were intubated with 0.8 mg/kg body weight 30 min before running each day. Red quadriceps (RQ) and white quadriceps (WQ) GLUT-4 protein concentrations of TR rats were significantly greater than those of CON and CL+TR rats. The RQ GLUT-4 protein concentration of the CL+TR rats was significantly greater than that of CON rats, but this difference did not occur in the WQ. GLUT-4 protein concentrations were not different between the CON and CL rats. The patterns of RQ and WQ GLUT-4 mRNA were similar to those of their respective GLUT-4 proteins. Rats receiving daily injections of propranolol (30 mg/kg body wt), a beta-adrenergic receptor antagonist, demonstrated no increase in GLUT-4 protein in RQ or WQ after 6 wk of exercise training. These results indicate that 1) clenbuterol can attenuate the increase in muscle GLUT-4 protein associated with exercise training and 2) this effect is likely mediated by a downregulation of the beta-adrenergic receptors.

Contraction-activated glucose uptake is normal in insulin-resistant muscle of the obese Zucker rat

1992 ◽  
Vol 73 (1) ◽  
pp. 382-387 ◽  
Author(s):  
J. T. Brozinick ◽  
G. J. Etgen ◽  
B. B. Yaspelkis ◽  
J. L. Ivy
Keyword(s):  
Muscle Contraction ◽  
Glucose Uptake ◽  
Fiber Type ◽  
Zucker Rats ◽  
Fiber Types ◽  
Glut 4 ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
Fast Twitch ◽  
White Gastrocnemius

The rates of muscle glucose uptake of lean and obese Zucker rats were assessed via hindlimb perfusion under basal conditions (no insulin), in the presence of a maximal insulin concentration (10 mU/ml), and after electrically stimulated muscle contraction in the absence of insulin. The perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H-(G)]glucose. Glucose uptake rates in the soleus (slow-twitch oxidative fibers), red gastrocnemius (fast-twitch oxidative-glycolytic fibers), and white gastrocnemius (fast-twitch glycolytic fibers) under basal conditions and after electrically stimulated muscle contraction were not significantly different between the lean and obese rats. However, the rate of glucose uptake during insulin stimulation was significantly lower for obese than for lean rats in all three fiber types. Significant correlations were found for insulin-stimulated glucose uptake and glucose transporter protein isoform (GLUT-4) content of soleus, red gastrocnemius, and white gastrocnemius of lean (r = 0.79) and obese (r = 0.65) rats. In contrast, the relationships between contraction-stimulated glucose uptake and muscle GLUT-4 content of lean and obese rats were negligible because of inordinately low contraction-stimulated glucose uptakes by the solei. These results suggest that maximal skeletal muscle glucose uptake of obese Zucker rats is resistant to stimulation by insulin but not to contractile activity. In addition, the relationship between contraction-stimulated glucose uptake and GLUT-4 content appears to be fiber-type specific.

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.

Lipolysis in isolated epididymal adipocytes from genetically obese Zucker rat treated with 3,5,3'-L-triiodothyronine

1990 ◽  
Vol 122 (3) ◽  
pp. 379-384 ◽  
Author(s):  
Halima Lebrazi ◽  
Philippe Chomard ◽  
Paul Dumas ◽  
Nicole Autissier
Keyword(s):  
Adipose Tissue ◽  
Single Injection ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Rat Adipose Tissue ◽  
Mild Hypothyroidism ◽  
Stimulation Of

Abstract. Glycerol released by isolated epididymal adipocytes was measured in 6-8 weeks old genetically obese (fa/fa) and lean (C.c.a/-) male Zucker rats, ip treated or not treated with T3 (0.46, 2.3 and 4.6 nmol/100 g in a single injection or 4.6 nmol · (100 g)−1 · day−1 for 5 days). In the non-treated rats, lipolysis was less stimulated by adrenalin or isoproterenol in obese than in lean rats, whereas it was stimulated by theophylline up to the same level in both kinds of rats. A single injection of the T3 (highest dose) increased isoproterenol-induced lipolysis in the lean but not in the obese rats. The 5-day T3 treatment caused a stimulation of the adrenalin- or isoproterenol-induced lipolysis in both kinds of rats. However, the stimulation was lower in the obese than in the lean rats. This treatment increased theophylline-induced lipolysis in the lean but not in the obese rats. It did not affect significantly the theophylline-induced lipolysis stimulated by adrenalin or isoproterenol in either obese or lean rats. These findings show that mild hypothyroidism of obese rat is partly responsible for the impaired sensitivity of its adipose tissue to lipolytic drugs. The apparently low T3 sensitivity of obese rat adipose tissue is discussed.

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