Clenbuterol-induced muscle growth: investigation of possible mediation by insulin

Abstract

The role of insulin as a possible mediator of the beta-adrenergic agonist stimulation of muscle growth was investigated. To exclude possible action of the beta-agonist on the pancreatic release of insulin, diabetes was induced in rats by a streptozotocin injection (100 mg/kg). Insulin levels were almost not detectable in these rats. Feeding either normal diet or diet containing the beta-adrenergic agonist clenbuterol (10 parts/million) did not alter plasma insulin concentrations. The effects of clenbuterol on muscle and weight gain were determined in diabetic rats given daily insulin replacement (D + I) and fed either a normal diet or clenbuterol-treated diet. Clenbuterol, fed for 1 wk, increased the wet weight of the gastrocnemius, soleus, and extensor digitorum longus muscles (15-23%) in both normal and D + I rats. Although clenbuterol increased body weight gain, it did not alter feed consumption and, therefore, feed efficiency (g gain/g food) was improved. Activities of cathepsin B and N-acetyl-beta-glucosaminidase, but not cathepsin D, were elevated in the soleus muscles of clenbuterol-treated rats. The clenbuterol-induced increase in muscle growth in the insulin-replaced diabetic rats indicated that this beta-adrenergic agonist effect was not mediated by an alteration of circulating levels of insulin, secondary to beta-agonist action on pancreatic insulin release.

Role of β-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease

“…Over the past 20 years there have been a multitude of studies demonstrating the growth-promoting actions of ␤-adrenoceptor stimulation in skeletal muscle (5,6,31,74,90,129,161,187,228,268,270,271,274,278,279,281,298,386,387,389,480,484). However, very little work has focused on the role of this pathway in normal muscle growth and development, muscle fiber regeneration after injury, or its involvement in pathological conditions where muscle wasting and weakness are indicated.…”

ß2-Agonists and cAMP inhibit protein degradation in isolated chick (Gallus domesticus) skeletal muscle

“…Thus, it was found that cimaterol decreases total protein degradation in isolated chick extensor digitorum communis (EDC) muscle (Rogers and Fagan, 1991), but increases proteolysis in cultured myotubes (Béchet et al, 1990). It has also been reported that cimaterol treatment reduces the cathepsin B activity in myotubes from chicken (Béchet et al, 1990), an effect not observed in rat gastrocnemius muscle (McElligott et al, 1987). On the other hand, other studies have shown that -agonists may not affect protein degradation directly, but increase protein synthesis in chicken muscle cell cultures (Shaoquan and Orcutt, 1991).…”

Effect of the Beta-Agonist Cimaterol on Growth and Composition of Neonatal Rats Selected for Large and Small Body Size

“…Most studies report no change or an increase in food intake or efficiency. Feed efficiency was increased in rats fed 10 ppm clenbuterol [9] and in normal or dystrophic mice injected with 2 mg/kg clenbuterol daily without af fecting energy intake [ 12], Administration of 1 mg/kg clenbuterol twice daily in young male rats produced increases in energy in take (23%), energy expenditure (26%) and weight gain (27%) [7], Changes in food in take and feed efficiency were variable in lambs treated with clenbuterol, with in creases in both gain and feed efficiency reaching statistical significance in only one trial using slightly older lambs fed 2 ppm clenbuterol [2], Clenbuterol (0.1 or 1.0 mg/kg milk replacer) had no effect on dry matter intake, average daily gain or feed con version ratio in veal calves [15]. The effects of clenbuterol on gain and feed efficiency may occur only in relatively mature animals [14], It is unlikely that a reduction in milk intake or feed efficiency explains the inhibi tion of growth in cimaterol-treated rats.…”