Kirby C R, Woodman C R, Woolridge D, Tischler M E
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Metabolism. 1992 Jul;41(7):793-9. doi: 10.1016/0026-0495(92)90323-3.
Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a beta-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular [IM] injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (Bmax) for [125I]iodo-(-)-pindolol in particulate preparations of unweighted (420.10(-18) mol/mg muscle) than of control or denervated muscles (285.10(-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished cAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +/- 6%, P less than .001). These results show that insulin affects cAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.
据报道，肌肉去负荷而非失神经支配会“保留”胰岛素受体，从而提高胰岛素敏感性。去负荷还会增加碳水化合物代谢的β-肾上腺素能反应。通过比较正常、去负荷3天或失神经支配的比目鱼肌中环状单磷酸腺苷（cAMP）的积累和β-肾上腺素能结合，进一步研究了这些差异特征。亚最大量的β-激动剂异丙肾上腺素在体外和体内（通过肌肉内[IM]注射）使去负荷肌肉中的cAMP积累增加的程度更大（P<0.05）。福斯高林或最大量的异丙肾上腺素在所有肌肉中具有相似的体外作用，表明去负荷后β-肾上腺素能敏感性增加。通过[125I]碘代（-）-吲哚洛尔在去负荷（420×10⁻¹⁸mol/mg肌肉）颗粒制剂中的受体密度（Bmax）高于对照或失神经支配的肌肉（285×10⁻¹⁸mol/mg肌肉），证实了敏感性增加。三个解离常数（Kd）值相似（20.3至25.8 pmol/L）。在去负荷3天期间，总结合能力（11.4 fmol/肌肉）没有变化，但失神经支配后减少了30%。这一结果分别说明了这两种萎缩模型中受体的“保留”和丢失。在糖尿病动物中，肌肉内注射胰岛素在茶碱存在的情况下，使去负荷肌肉中的cAMP积累减少（-66%±2%）比对照组（-42%±6%，P<0.001）更多。这些结果表明胰岛素影响肌肉中cAMP的形成，并支持去负荷萎缩后体内胰岛素反应更大。这些各种数据支持溶酶体蛋白水解在失神经支配萎缩而非去负荷萎缩中起作用。
