Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats

Torgan, C. E.; Brozinick, Joseph T.; Banks, E. A.; Cortez, M. Y.; Wilcox, Richard E.; Ivy, John L.

doi:10.1152/ajpendo.1993.264.3.e373

Cited by 34 publications

(49 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hyperinsulinemic human beings and rodents submitted to different types of exercises show reduction of blood insulin levels, even though the decrease rate depends on duration and intensity of training (Torgan et al 1993, Kretschmer et al 2005. It has been suggested that decrease in fat tissue accumulation is related to normalization of fasting insulin levels and, it is well known, insulin has been identified as an adiposity signal, like leptin (Schwartz & Porte 2005).…”

Section: Discussionmentioning

confidence: 99%

Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium l-glutamate-obesity in mice

Andreazzi¹,

Scomparin²,

Mesquita³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

Swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, but this was not observed when exercise training was applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Low-intensity swimming training started at an early age and was undertaken to observe glycemic control in hypothalamic-obese mice produced by neonatal treatment with monosodium L-glutamate (MSG). Whereas MSG and control mice swam for 15 min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Perigonadal fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Fresh isolated pancreatic islets were used to test glucose-induced insulin release and total catecholamine from the adrenal glands was measured. Mice were also submitted to intraperitoneal glucose tolerance test. MSG-obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance. Severe reduction of adrenal catecholamines content has also been reported. Besides, the inhibition of fat tissue accretion, exercise caused normalization of insulin blood levels and glycemic control. The pancreatic islets of obese mice, with impaired glucose-induced insulin secretion, were recovered after swimming exercises. Adrenal catecholamine content was increased by swimming. Results show that attenuation of MSG-hypothalamic obesity onset is caused, at least in part, by modulation of sympathoadrenal axis activity imposed by early exercise, which may be associated with subsequent glucose metabolism improvement.

show abstract

Section: Discussionmentioning

confidence: 99%

Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium l-glutamate-obesity in mice

Andreazzi¹,

Scomparin²,

Mesquita³

et al. 2009

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In another animal model (insulin-resistant obese Zucker rat), clenbuterol did not affect GLUT4 protein and mRNA in red and white skeletal muscle (38,52) but improved glucose tolerance (64). On the other hand, glucose uptake and transport were not different in different muscle fiber types between clenbuterol-treated obese and control obese rats (64 -66).…”

Section: R379mentioning

confidence: 92%

“…In contrast to these unusual responses of clenbuterol treatment with respect to changes in PGC-1␣ mRNA (19,47), our present results are consistent with studies showing that in skeletal muscle, clenbuterol decreases mitochondrial enzyme activity and contents and increases glycolytic enzyme activity (present study; 35,49,53), and our observed reduction in PGC-1␣ protein and mRNA is fully consistent with such changes. Also, long-term clenbuterol administration decreased ␤-adrenergic receptor concentration in skeletal muscle (64,65), effects that may inhibit the transcription of PGC-1␣, thereby contributing to reduced mitochondrial content and capacity in skeletal muscle. Thus, clenbuterol-induced ␤2 adrenergic stimulation by a single injection appears to increase PGC-1␣ transcription (24,48), whereas in the current study, 3 wk of clenbuterol administration decreases PGC-1␣ protein and mRNA, presumably via the decreased ␤2 adrenergic stimulation due to long-term clenbuterol administration (64,65).…”

Section: R381 Clenbuterol Reduces Mitochondrial Substrate Oxidationmentioning

confidence: 99%

“…Also, long-term clenbuterol administration decreased ␤-adrenergic receptor concentration in skeletal muscle (64,65), effects that may inhibit the transcription of PGC-1␣, thereby contributing to reduced mitochondrial content and capacity in skeletal muscle. Thus, clenbuterol-induced ␤2 adrenergic stimulation by a single injection appears to increase PGC-1␣ transcription (24,48), whereas in the current study, 3 wk of clenbuterol administration decreases PGC-1␣ protein and mRNA, presumably via the decreased ␤2 adrenergic stimulation due to long-term clenbuterol administration (64,65). Further study is needed to clarify the time course of change in PGC-1␣ transcription.…”

Section: R381 Clenbuterol Reduces Mitochondrial Substrate Oxidationmentioning

confidence: 99%

See 1 more Smart Citation

Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle

Hoshino

Yoshida

Holloway

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

a ␤2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol 302: R373-R384, 2012. First published November 9, 2011 doi:10.1152/ajpregu.00183.2011.-Clenbuterol, a ␤2-adrenergic agonist, reduces mitochondrial content and enzyme activities in skeletal muscle, but the mechanism involved has yet to be identified. We examined whether clenbuterol-induced changes in the muscles' metabolic profile and the intrinsic capacity of mitochondria to oxidize substrates are associated with reductions in the nuclear receptor coactivator PGC-1 alpha and/or an increase in the nuclear corepressor RIP140. In rats, clenbuterol was provided in the drinking water (30 mg/l). In 3 wk, this increased body (8%) and muscle weights (12-17%). In red (R) and white (W) muscles, clenbuterol induced reductions in mitochondrial content (citrate synthase: R, 27%; W, 52%; cytochrome-c oxidase: R, 24%; W, 34%), proteins involved in fatty acid transport (fatty acid translocase/CD36: R, 36%; W, 35%) and oxidation [␤-hydroxyacyl CoA dehydrogenase (␤-HAD): R, 33%; W, 62%], glucose transport (GLUT4: R, 8%; W, 13%), lactate transport monocarboxylate transporter (MCT1: R, 61%; W, 37%), and pyruvate oxidation (PDHE1␣, R, 18%; W, 12%). Concurrently, only red muscle lactate dehydrogenase activity (25%) and MCT4 (31%) were increased. Palmitate oxidation was reduced in subsarcolemmal (SS) (R, 30%; W, 52%) and intermyofibrillar (IMF) mitochondria (R, 17%; W, 44%) along with reductions in ␤-HAD activity (SS: R, 17%; W, 51%; IMF: R, 20%; W, 57%). Pyruvate oxidation was only reduced in SS mitochondria (R, 20%; W, 28%), but this was not attributable solely to PDHE1␣, which was reduced in both SS (R, 21%; W, 20%) and IMF mitochondria (R, 15%; W, 43%). These extensive metabolic changes induced by clenbuterol were associated with reductions in PGC-1␣ (R, 37%; W, 32%) and increases in RIP140 (R, 23%; W, 21%). This is the first evidence that clenbuterol appears to exert its metabolic effects via simultaneous and reciprocal changes in the nuclear receptor coactivator PGC-1␣ and the nuclear corepressor RIP140. mitochondria; oxidative capacity CLENBUTEROL, A ␤2-ADRENERGIC agonist, induces skeletal and cardiac muscle hypertrophy, due to increased protein synthesis and a concomitant decrease in protein degradation in this tissue (2,46,50). This ␤2-adrenergic agonist is a commonly prescribed bronchodilator treatment for asthmatic patients, while its anabolic properties have led to its illegal use in animal meat production and doping in sports. Nevertheless, it has been found that the treatment with this clenbuterol provoked deleterious effects on the cardiovascular system (1) and bone mass (12), as well as impairing exercise performance (16,32). The mechanistic bases of the maladaptations induced by clenbuterol in skeletal muscle remain largely unknown.Chronic administration of clenbuterol induces the transition from slow to fast muscle fiber types (35,49,53,56) a...

show abstract

“…Therefore, in the next series of experiments we assessed the impact of the amelioration of insulin resistance and the reduction in the levels of insulinaemia on the amounts of farnesylated p21Ras. One group of Zucker rats (Table 1, Group 4) was exercised for 7 weeks, 90 min per day, whereas another group of Zucker rats (Table 1, Group 5) was treated with clenbuterol, a beta-adrenergic agonist that has previously been shown to improve insulin sensitivity in Zucker rats [16,17]. Both exercise and the treatment with clenbuterol reduced the levels of insulinaemia in obese Zucker rats ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

Increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals

et al. 1999

Self Cite

View full text Add to dashboard Cite

Activation of the Ras signalling pathway by GTP loading of Ras proteins is the critical step that connects the events at the plasma membrane with cellular and nuclear responses [1]. The replacement of p21Ras-bound GDP with GTP is facilitated by guanine nucleotide exchange factors that convert inactive p21Ras-GDP proteins into the active p21Ras-GTP conformation, enabling p21Ras-GTP to transduce external signals to internal events [2,3]. Conversely, the return of the active form of p21Ras into the inactive form is preceded by the hydrolysis of p21Ras-GTP to GDP [1±4], a process that is not only intrinsic to Ras proteins but also increased by the GTPase activating protein (GAP).Only post-translationally modified Ras proteins (those that are farnesylated and carboxymethylated) are translocated to the plasma membrane whereby they can be activated by the guanine nucleotide exchange factors [5]. Farnesylation of p21Ras is catalyzed by the enzyme farnesyltransferase (FTase) [6,7] and is an obligatory initial step that targets Ras proteins to the plasma membrane for future activa- Diabetologia (1999) Summary We have recently demonstrated that insulin activates farnesyltransferase (FTase) and thereby increases the amounts of cellular farnesylated p21Ras in 3T3-L1 fibroblasts, adipocytes and vascular smooth muscle cells. We postulated that hyperinsulinaemia might considerably increase the the cellular pool of farnesylated p21Ras available for activation by other growth factors. To examine the role of in vivo hyperinsulinaemia in regulating farnesylated p21Ras, we measured the amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals. Liver, aorta, and skeletal muscle of ob/ob mice, and mice made obese and hyperinsulinaemic by injection of gold-thioglucose contained greater amounts of farnesylated p21Ras than tissues of their lean normoinsulinaemic counterparts. Similarly, farnesylated p21Ras was increased (67 vs 35 % in control animals, p < 0.01) in the livers of hyperinsulinaemic Zucker rats (fa/fa). Reduction of hyperinsulinaemia by exercise training (2 h/day for 7±8 weeks) resulted in decreases in the amounts of farnesylated p21Ras in these animals. Increased farnesylated p21Ras in hyperinsulinaemic animals reflected increasing increments in the activity of FTase in ob/ob mice (2-fold increase) and fa/fa Zucker rats (3.5-fold increase), while the total amounts of Ras proteins remained unchanged. In contrast to insulin-resistant hyperinsulinaemic animals, denervated insulin-resistant rat soleus muscle (in the presence of normoinsulinaemia) showed normal amounts of farnesylated p21Ras. In summary, these data confirm increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals. [Diabetologia (1999) 42: 310±316]

show abstract

Exercise training and clenbuterol reduce insulin resistance of obese Zucker rats

Cited by 34 publications

References 5 publications

Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium l-glutamate-obesity in mice

Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium l-glutamate-obesity in mice

Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle

Increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals

Contact Info

Product

Resources

About