ABSTRACT
Skeletal muscle development, nutrient uptake, and nutrient utilization is largely coordinated by growth hormone (GH) and its downstream effectors, in particular, IGF-1. However, it is not clear which effects of GH on skeletal muscle are direct and which are secondary to GH-induced IGF-1 expression. Thus, we generated mice lacking either GH receptor (GHR) or IGF-1 receptor (IGF-1R) specifically in skeletal muscle. Both exhibited impaired skeletal muscle development characterized by reductions in myofiber number and area as well as accompanying deficiencies in functional performance. Defective skeletal muscle development, in both GHR and IGF-1R mutants, was attributable to diminished myoblast fusion and associated with compromised nuclear factor of activated T cells import and activity. Strikingly, mice lacking GHR developed metabolic features that were not observed in the IGF-1R mutants, including marked peripheral adiposity, insulin resistance, and glucose intolerance. Insulin resistance in GHR-deficient myotubes derived from reduced IR protein abundance and increased inhibitory phosphorylation of IRS-1 on Ser 1101. These results identify distinct signaling pathways through which GHR regulates skeletal muscle development and modulates nutrient metabolism.
Subject(s)
Insulin Resistance , Insulin/metabolism , Muscle, Skeletal/growth & development , Muscle, Skeletal/metabolism , Receptors, Somatotropin/metabolism , Signal Transduction/physiology , Animals , Behavior, Animal , Cells, Cultured , Eating , Growth Hormone/metabolism , Humans , Interleukin-4/metabolism , Membrane Fusion/physiology , Mice , Mice, Knockout , Motor Activity , Muscle, Skeletal/cytology , Myoblasts/cytology , Myoblasts/metabolism , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/metabolism , Receptors, Somatotropin/geneticsABSTRACT
PURPOSE: The purpose of this study was to measure the variability of torque produced by a population of mechanical torque-limiting devices in clinical service in a US dental school. The torque-limiting devices were divided into two categories according to their mode of action: toggle-type and beam wrenches. Proper action of these devices is essential for calibrated delivery of preload to implant prosthetic screws. MATERIALS AND METHODS: Seventeen torque-limiting devices (35 Ncm) were obtained from graduate prosthodontic, predoctoral, and faculty practice clinics. Nine of these were toggle-type devices, and eight were beam-type wrenches. Torque from each wrench was measured using an MGT electronic torque meter. Wrenches were tested in two modes, slow (over 4 seconds) and fast (over 1 second). RESULTS: Toggle-type torque wrenches produced a mean (+/- SD) torque of 38.1 +/- 16.0 Ncm; beam-type wrenches produced 32.8 +/- 1.1 Ncm. These results were not significantly different. When tested in fast mode (1 second), toggle-type wrenches produced 28.0 +/- 9.6 Ncm; in the slow mode (4 seconds) they produced significantly more force, 36.6 +/- 14.0 Ncm (p < 0.001). Beam-type wrenches produced 33.2 +/- 1.1 Ncm and 32.8 +/- 1.1 Ncm in fast and slow modes, respectively. CONCLUSIONS: Both types of wrenches tested were capable of producing accurate torque values; however, variability was higher in the toggle-type group. Some toggle-type torque wrenches in clinical service delivered unacceptably high torque values. It is recommended that clinicians calibrate toggle-type wrenches frequently. Torque wrenches should be activated slowly, over 4 seconds, when using a correctly calibrated toggle-type wrench.
