scholarly journals Proposed mechanism for increased insulin-mediated glucose transport in adipose cells from young, obese Zucker rats. Large intracellular pool of glucose transporters.

1985 ◽  
Vol 260 (4) ◽  
pp. 2197-2201 ◽  
Author(s):  
M Guerre-Millo ◽  
M Lavau ◽  
J S Horne ◽  
L J Wardzala
Keyword(s):  
Glucose Transport ◽  
Glucose Transporters ◽  
Zucker Rats ◽  
Intracellular Pool ◽  
Obese Zucker Rats ◽  
Adipose Cells

Physical training of lean and genetically obese Zucker rats: effect on fat cell metabolism

1982 ◽  
Vol 243 (5) ◽  
pp. E418-E426 ◽  
Author(s):  
L. J. Wardzala ◽  
M. Crettaz ◽  
E. D. Horton ◽  
B. Jeanrenaud ◽  
E. S. Horton
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Cell Metabolism ◽  
Insulin Binding ◽  
Zucker Rats ◽  
Fat Cell ◽  
Obese Rats ◽  
Increased Sensitivity ◽  
Obese Zucker Rats ◽  
Adipose Cells

The effects of 6-wk treadmill training program on the metabolism of isolated adipose cells from obese (fa/fa) and lean (Fa/?) Zucker rats were studied. Glucose metabolism and transport, insulin binding, and lipolysis were measured in adipose cells prepared from sedentary control and exercise-trained (ET) lean and/or obese rats. Two- to threefold increases in glucose metabolism were observed in cells from lean and obese ET rats compared with their respective controls. However, the insulin concentrations giving half-maximal stimulation (measuring insulin sensitivity) did not change (approximately 8 microunits/ml in lean and approximately 45 microunits/ml in obese rats). In lean ET rats, glucose transport and maximal glucose metabolic capacity (transport not rate-limiting) were increased twofold and sensitivity of lipolysis to epinephrine was increased three- to fourfold. These were not measured in obese rats. The results suggest that training of both lean and obese Zucker rats increases glucose utilization in adipose cells by increasing both glucose transport and intracellular glucose metabolism. Increased triglyceride turnover is also suggested by the increased sensitivity of lipolysis to epinephrine.

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.

Exercise training increases the number of glucose transporters in rat adipose cells

1989 ◽  
Vol 257 (4) ◽  
pp. E520-E530
Author(s):  
M. F. Hirshman ◽  
L. J. Wardzala ◽  
L. J. Goodyear ◽  
S. P. Fuller ◽  
E. D. Horton ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Glucose Transport ◽  
Glucose Transporters ◽  
Membrane Transporters ◽  
Control Group ◽  
Transport Activity ◽  
Insulin Stimulation ◽  
Adipose Cell ◽  
Adipose Cell Size ◽  
Adipose Cells

We studied the mechanism for the increase in glucose transport activity that occurs in adipose cells of exercise-trained rats. Glucose transport activity, glucose metabolism, and the subcellular distribution of glucose transporters were measured in adipose cells from rats raised in wheel cages for 6 wk (mean total exercise 350 km/rat), age-matched sedentary controls, and young sedentary controls matched for adipose cell size. Basal rates of glucose transport and metabolism were greater in cells from exercise-trained rats compared with young controls, and insulin-stimulated rates were greater in the exercise-trained rats compared with both age-matched and young controls. The numbers of plasma membrane glucose transporters were not different among groups in the basal state; however, with insulin stimulation, cells from exercise-trained animals had significantly more plasma membrane transporters than young controls or age-matched controls. Exercise-trained rats also had more low-density microsomal transporters than control rats in the basal state. When the total number of glucose transporters/cell was calculated, the exercise-trained rats had 42% more transporters than did either control group. These studies demonstrate that the increased glucose transport and metabolism observed in insulin-stimulated adipose cells from exercise-trained rats is due, primarily, to an increase in the number of plasma membrane glucose transporters translocated from an enlarged intracellular pool.

scholarly journals Cycloheximide decreases glucose transporters in rat adipocyte plasma membranes without affecting insulin-stimulated glucose transport

1988 ◽  
Vol 251 (2) ◽  
pp. 491-497 ◽  
Author(s):  
S Matthaei ◽  
J M Olefsky ◽  
E Karnieli
Keyword(s):  
Protein Synthesis ◽  
Glucose Transport ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Glucose Transporters ◽  
Electrophoretic Analysis ◽  
Adipocyte Plasma Membranes ◽  
Inhibitor Of Protein Synthesis ◽  
Adipose Cells

This study examines the relationship between insulin-stimulated glucose transport and insulin-induced translocation of glucose transporters in isolated rat adipocytes. Adipose cells were incubated with or without cycloheximide, a potent inhibitor of protein synthesis, for 60 min and then for an additional 30 min with or without insulin. After the incubation we measured 3-O-methylglucose transport in the adipose cells, and subcellular membrane fractions were prepared. The numbers of glucose transporters in the various membrane fractions were determined by the cytochalasin B binding assay. Basal and insulin-stimulated 3-O-methylglucose uptakes were not affected by cycloheximide. Furthermore, cycloheximide affected neither Vmax. nor Km of insulin-stimulated 3-O-methylglucose transport. In contrast, the number of glucose transporters in plasma membranes derived from cells preincubated with cycloheximide and insulin was markedly decreased compared with those from cells incubated with insulin alone (10.5 +/- 0.8 and 22.2 +/- 1.8 pmol/mg of protein respectively; P less than 0.005). The number of glucose transporters in cells incubated with cycloheximide alone was not significantly different compared with control cells. SDS/polyacrylamide-gel-electrophoretic analysis of [3H]cytochalasin-B-photolabelled plasma-membrane fractions revealed that cycloheximide decreases the amount of labelled glucose transporters in insulin-stimulated membranes. However, the apparent molecular mass of the protein was not changed by cycloheximide treatment. The effect of cycloheximide on the two-dimensional electrophoretic profile of the glucose transporter in insulin-stimulated low-density microsomal membranes revealed a decrease in the pI-6.4 glucose-transporter isoform, whereas the insulin-translocatable isoform (pI 5.6) was decreased. Thus the observed discrepancy between insulin-stimulated glucose transport and insulin-induced translocation of glucose transporters strongly suggests that a still unknown protein-synthesis-dependent mechanism is involved in insulin activation of glucose transport.

scholarly journals Thrombin-induced translocation of GLUT3 glucose transporters in human platelets

1997 ◽  
Vol 328 (2) ◽  
pp. 511-516 ◽  
Author(s):  
R. Lynn SORBARA ◽  
Theresa M. DAVIES-HILL ◽  
Ellen M. KOEHLER-STEC ◽  
J. Susan VANNUCCI ◽  
K. McDonald HORNE ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Human Platelets ◽  
Half Time ◽  
Transport Activity ◽  
Kinase C ◽  
Adipose Cells

Platelets derive most of their energy from anaerobic glycolysis; during activation this requirement rises approx. 3-fold. To accommodate the high glucose flux, platelets express extremely high concentrations (155±18 pmol/mg of membrane protein) of the most active glucose transporter isoform, GLUT3. Thrombin, a potent platelet activator, was found to stimulate 2-deoxyglucose transport activity 3-5-fold within 10 min at 25 °C, with a half-time of 1-2 min. To determine the mechanism underlying the increase in glucose transport activity, an impermeant photolabel, [2-3H]2N-4-(1-azi-2,2,2-trifluoethyl)benzoyl-1,3,-bis-(d-mannose-4-ylozy)-2-propylamine, was used to covalently bind glucose transporters accessible to the extracellular milieu. In response to thrombin, the level of transporter labelling increased 2.7-fold with a half-time of 1-2 min. This suggests a translocation of GLUT3 transporters from an intracellular site to the plasma membrane in a manner analogous to that seen for the translocation of GLUT4 in insulin-stimulated rat adipose cells. To investigate whether a similar signalling pathway was involved in both systems, platelets and adipose cells were exposed to staurosporin and wortmannin, two inhibitors of GLUT4 translocation in adipose cells. Thrombin stimulation of glucose transport activity in platelets was more sensitive to staurosporin inhibition than was insulin-stimulated transport activity in adipose cells, but it was totally insensitive to wortmannin. This indicates that the GLUT3 translocation in platelets is mediated by a protein kinase C not by a phosphatidylinositol 3-kinase mechanism. In support of this contention, the phorbol ester PMA, which specifically activates protein kinase C, fully stimulated glucose transport activity in platelets and was equally sensitive to inhibition by staurosporin. This study provides a cellular mechanism by which platelets enhance their capacity to import glucose to fulfil the increased energy demands associated with activation.

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.

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