Insulin resistance of obese Zucker rats exercise trained at two different intensities

Cortez, M. Y.; Torgan, C. E.; Brozinick, Joseph T.; Ivy, John L.

doi:10.1152/ajpendo.1991.261.5.e613

Cited by 96 publications

(105 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…32 This could help to normalize glycaemia: exercise is known to help lower hyperglycaemia in the obese. 33 Second, the lactate produced may be used for gluconeogenesis, or may be used as alternate substrate by a number of other tissues. 3 In any case the increase in acidity and the fair use and availability of glucose prevent the mobilization of lipids and ketoacidosis.…”

Section: Discussionmentioning

confidence: 99%

Lactate-bicarbonate interrelationship during exercise and recovery in lean and obese Zucker rats

et al. 1997

View full text Add to dashboard Cite

OBJECTIVE: To determine the relationship between muscle-derived lactate at fatigue and earlier onset of fatigue in the obese rat subjected to intense exercise. DESIGN: Rats were subjected to a short, intense exercise protocol on a treadmill. Blood was drawn from hind leg vein and artery during exercise and up to 1 h afterwards. Assuming an exercise respiratory quotient of 1.0, the extra carbon dioxide released was computed and assumed to be displaced by equimolar amounts of lactic acid produced by the rat during exercise. SUBJECTS: Conscious female adult Zucker lean and Zucker obese rats. MEASUREMENTS: Oxygen consumption and carbon dioxide release. Lactate and bicarbonate levels in hind leg venous and arterial blood; balances were estimated by measuring blood¯ow with¯uorescent microspheres. Lactate levels in periovaric white adipose tissue were also measured. RESULTS: Muscle released, during exercise and post exercise roughly 2.3 mmol lactate in lean rats and 2.6 mmol in obese ones. Of these amounts, hind leg lactate release accounted for 0.40 mmol in lean rats and only 0.11 in the obese ones, which showed a release of acid (mainly lactate) elsewhere in the rats totalling about 19.9 mmol CO 2 in lean rats and 4.4% in the obese ones; that is both hind quarters accounted for only 17.2% of all lactate produced in the lean rats and 4.4% in the obese ones. The amount of lactate produced by the rats was roughly similar. White adipose tissue lactate levels (in the basal state and after exercise) were much higher than could be expected from blood sources alone, indicating an active production of lactate. CONCLUSION: Fatigue appears earlier in the obese rats than in lean ones because of loss of buffering ability caused by massive extra-muscular glycolysis (probably in adipose tissue) and lactate production triggered by exercise-induced adrenergic stimulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Lactate-bicarbonate interrelationship during exercise and recovery in lean and obese Zucker rats

et al. 1997

View full text Add to dashboard Cite

show abstract

“…either exercise training in lean or obese animals [43], or rosiglitazone treatment [44,45]. However, these changes were observed after many weeks of treatment, whereas Pgc-1α transfection induced changes within 2 weeks.…”

Section: Characterisation Of Lean and Obese Zucker Ratsmentioning

confidence: 99%

Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

et al. 2010

View full text Add to dashboard Cite

Aims/hypothesis Reductions in peroxisome proliferatoractivated receptor gamma, coactivator 1 alpha (PGC-1α) levels have been associated with the skeletal muscle insulin resistance. However, in vivo, the therapeutic potential of PGC-1α has met with failure, as supra-physiological overexpression of PGC-1α induced insulin resistance, due to fatty acid translocase (FAT)-mediated lipid accumulation. Based on physiological and metabolic considerations, we hypothesised that a modest increase in PGC-1α levels would limit FAT upregulation and improve lipid metabolism and insulin sensitivity, although these effects may differ in lean and insulin-resistant muscle. Methods Pgc-1α was transfected into lean and obese Zucker rat muscles. Two weeks later we examined mitochondrial biogenesis, intramuscular lipids (triacylglycerol, diacylglycerol, ceramide), GLUT4 and FAT levels, insulin-stimulated glucose transport and signalling protein phosphorylation (thymoma viral proto-oncogene 2 [Akt2], Akt substrate of 160 kDa [AS160]), and fatty acid oxidation in subsarcolemmal and intermyofibrillar mitochondria. Results Electrotransfection yielded physiologically relevant increases in Pgc-1α (also known as Ppargc1a) mRNA and protein (∼25%) in lean and obese muscle. This induced mitochondrial biogenesis, and increased FAT and GLUT4 levels, insulin-stimulated glucose transport, and Akt2 and AS160 phosphorylation in lean and obese animals, while bioactive intramuscular lipids were only reduced in obese muscle. Concurrently, PGC-1α increased palmitate oxidation in subsarcolemmal, but not in intermyofibrillar mitochondria, in both groups. In obese compared with lean animals, the PGC-1α-induced improvement in insulin-stimulated glucose transport was smaller, but intramuscular lipid reduction was greater. Conclusions/interpretations Increases in PGC-1α levels, similar to those that can be induced by physiological stimuli, altered intramuscular lipids and improved fatty acid oxidation, insulin signalling and insulin-stimulated glucose transport, albeit to different extents in lean and insulinresistant muscle. These positive effects are probably attributable to limiting the PGC-1α-induced increase in FAT, thereby preventing bioactive lipid accumulation as has occurred in transgenic PGC-1α animals.

show abstract

“…Total areas under the curve (AUC) for these glucose and insulin responses and the glucose-insulin index (the product of glucose AUC and insulin AUC; a reduction in this value reflects an increase in whole-body insulin sensitivity 25 ), are presented in Figure 1, bottom. Whereas the reductions in the obese group treated with 25 mg/kg irbesartan did not reach statistical significance, animals treated with 50 mg/kg irbesartan displayed significant reductions in glucose (13%; PϽ0.05) and insulin (15%; PϽ0.05) AUC.…”

Section: Acute Administration Of Irbesartanmentioning

confidence: 99%

Selective Angiotensin II Receptor Antagonism Reduces Insulin Resistance in Obese Zucker Rats

et al. 2001

View full text Add to dashboard Cite

Abstract-Effects of oral administration of the angiotensin II receptor antagonist (selective AT 1 -subtype) irbesartan on glucose tolerance and insulin action on skeletal-muscle glucose transport were assessed in the insulin-resistant obese Zucker rat. In the acute study, obese rats received either vehicle (water) or irbesartan 1 hour before the experiment. Although irbesartan had no effect on glucose transport (2-deoxyglucose uptake) in the epitrochlearis muscle, which consists mainly of type IIb fibers, acute angiotensin II receptor antagonism led to a dose-dependent increase in insulin action in the predominantly type I soleus muscle. Irbesartan at 25 and 50 mg/kg induced significant increases (41% and 50%, respectively; PϽ0.05) in insulin-mediated glucose transport. Moreover, these acute irbesartan-induced improvements in soleus-muscle glucose transport were associated with enhancements in whole-body insulin sensitivity (rϭϪ0.732; PϽ0.05), as assessed during an oral glucose tolerance test. After chronic administration of irbesartan (21 days at 50 mg · kg), glucose tolerance was enhanced further, and insulin-mediated glucose transport was significantly elevated in both epitrochlearis (32%) and soleus (73%) muscle. Chronic angiotensin II receptor antagonism was associated with significant increases in glucose transporter-4 (GLUT-4) protein expression in soleus (22%) and plantaris (20%) muscle and myocardium (15%). Chronic irbesartan-induced increases in whole-body insulin sensitivity were associated with increased insulin-mediated glucose transport in both epitrochlearis (rϭϪ0.677; PϽ0.05) and soleus (rϭϪ0.892; PϽ0.05) muscle. In summary, angiotensin II receptor (AT 1 -subtype) antagonism, either acutely or chronically, improves glucose tolerance, at least in part because of an enhancement in skeletal-muscle glucose transport, and the effect of chronic angiotensin II receptor antagonism on type I skeletal-muscle glucose uptake is associated with an increase in GLUT-4 protein expression. Key Words: irbesartan Ⅲ glucose Ⅲ muscle, skeletal Ⅲ transport, glucose Ⅲ rats, Zucker Ⅲ receptors, angiotensin I ndividuals with essential hypertension frequently display a clustering of additional atherogenic risk factors, including insulin resistance of skeletal-muscle glucose uptake, hyperinsulinemia, dyslipidemia, and central adiposity, in a condition described as "insulin resistance syndrome." 1 Angiotensin (Ang) II is a potent vasoconstrictor and can contribute to the pathogenesis of hypertension. 2 Reductions in formation of Ang II, as results from treatment with ACE inhibitors or inhibition of the cellular actions of Ang II by the use of specific Ang II (AT 1 -subtype) antagonists, are effective interventions for lowering blood pressure. [3][4][5] Although both animal model studies 6 -12 and clinical investigations 6,[13][14][15][16][17][18] have demonstrated that ACE inhibitor treatment can ameliorate peripheral insulin resistance, the role of a specific reduction in Ang II action on whole-body and skeletal-muscle ins...

show abstract

Insulin resistance of obese Zucker rats exercise trained at two different intensities

Cited by 96 publications

References 22 publications

Lactate-bicarbonate interrelationship during exercise and recovery in lean and obese Zucker rats

Lactate-bicarbonate interrelationship during exercise and recovery in lean and obese Zucker rats

Increased levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) improve lipid utilisation, insulin signalling and glucose transport in skeletal muscle of lean and insulin-resistant obese Zucker rats

Selective Angiotensin II Receptor Antagonism Reduces Insulin Resistance in Obese Zucker Rats

Contact Info

Product

Resources

About