Impaired Translocation of GLUT4 Results in Insulin Resistance of Atrophic Soleus Muscle

Abstract

Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

Hindlimb Immobilization, But Not Castration, Induces Reduction of Undercarboxylated Osteocalcin Associated With Muscle Atrophy in Rats

“…For instance, 10-day limb immobilization in rats led to a significant reduction in p-AMPK expression in red gastrocnemius muscle compared to the contralateral leg. (46,51) These incompatible results fit the contradictory role of AMPK in cell fate in skeletal muscles. (49) In humans, patients with critical myopathy showed decreased AMPK activity in skeletal muscles compared with healthy controls.…”

“…However, unchanged or even a higher AMPK activity during muscle atrophy has also been reported. (46,51) These incompatible results fit the contradictory role of AMPK in cell fate in skeletal muscles. On one hand, high activity of AMPK induces membrane GLUT4 expression as well as mitochondrial biogenesis, benefiting muscle glucose metabolism and cell growth.…”

Immobilization in diabetic rats results in altered glucose tolerance A model of reduced locomotion/activity in diabetes

“…Since the major manifestation of insulin resistance is a reduced stimulated glucose disposal by skeletal muscle, we focused our attention on the effects of the immobilization on glucose transport in unloaded soleus muscle of diabetic rats. It has been previously demonstrated that insulin‐ and contraction‐stimulated glucose uptake decreases in atrophic soleus muscle of tail‐suspended rats [31]. Insulin resistance in skeletal muscle was due to the attenuated expression level of the glucose transport GLUT4 with or without insulin‐stimulation, decreased GLUT4 activity or impaired GLUT4 translocation to sarcolemma [31].…”

“…It has been previously demonstrated that insulin‐ and contraction‐stimulated glucose uptake decreases in atrophic soleus muscle of tail‐suspended rats [31]. Insulin resistance in skeletal muscle was due to the attenuated expression level of the glucose transport GLUT4 with or without insulin‐stimulation, decreased GLUT4 activity or impaired GLUT4 translocation to sarcolemma [31]. Since the reduced GLUT4 content in immobilized muscle likely contributes to the deleterious impact on the altered glucose metabolism of diabetic animals [32], the gene expression of GLUT4 in the red soleus muscle was assessed by RT‐PCR analysis.…”

Estrogen treatment effects on rats soleus muscles' glycogen content, extracellular matrix and cross-sectional area

“…Extracellular matrix remodeling can affect the extent of axonal growth during reinnervation because collagen fibers can be a barrier and delay the diffusion of nerve growth hormone (SCHIAFFINO, KUROSE, KAWAMATA et al, 2013). These physiological events reduce glucose uptake and metabolism, predisposing muscle fibers to atrophy and to peripheral insulin resistance (LO, RUSSELL, TAYLOR et al, 1970;CODERRE, MONFAR, CHEN et al, 1992;HENRIKSEN, RODNICK, MONDON et al, 1997;XU, SONG, ZHANG et al, 2015).…”