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The effect of long‐term hindlimb denervation on glucose transport in a mouse model
Author(s) -
Callahan Zachary,
Bartos Amanda,
Cassell Emily,
Schaeffer Paul
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1106.2
Subject(s) - denervation , hindlimb , muscle atrophy , sciatic nerve , medicine , atrophy , sham surgery , glut4 , tibialis anterior muscle , gastrocnemius muscle , tibial nerve , skeletal muscle , endocrinology , anatomy , surgery , anesthesia , insulin , pathology , glucose transporter , stimulation , alternative medicine
We investigated the role of muscle activity in maintaining normal glucose homeostasis. Our model, denervation via transection of the sciatic nerve is an extreme model of inactivity for the hind‐limb muscles while allowing normal function of other tissues. A pilot study was employed in which either a sham surgery (in which the sciatic nerve was exposed but not cut) or transection surgery was performed. Following surgery, mice were sacrificed either 3 days, 10 days, 4 weeks, or 8 weeks post surgery. Gastrocnemius, soleus, and tibialis anterior muscles were collected from both transected and sham limbs, weighed and frozen for gene expression analysis. For all muscles, there was no difference in mass comparing sham and transected limbs at 3‐days post surgery, but the other three groups demonstrated a significant (P < 0.05) reduction in mass following transection. Lipid content of gastrocnemius muscle was not significantly different (P >0.05) between sham or transection groups at 8 weeks post surgery. There was no significant difference (P < 0.05) in either the Akt/Actin ratio or the GLUT4/Actin ratio comparing sham or transected groups at either 4 or 8 weeks post surgery. Immediately following denervation, there is a rapid atrophy of muscle tissue via necrotic and apoptotic mechanisms but atrophy ceases before 4 weeks post surgery and the remaining muscle mass is maintained thereafter. Although numerous studies have demonstrated a significant decrease in GLUT4 as well as other insulin signaling pathway components after short‐term (1, 3, and 7 day) denervation as well as a reduction in glucose uptake, we believe that atrophy may interfere with other physiological functions and prevent an accurate assessment of the role that inactivity plays in the ability to maintain normal glucose homeostasis. This work was supported by a grant from the NIH, award number 1R15DK085 497‐01A1.