Diabetes Alters Contraction‐Induced Mitogen Activated Protein Kinase Activation in the Rat Soleus and Plantaris

Abstract

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and p38 phosphorylation to a single bout of contractile stimuli were greater in the plantaris of obese animals. Jnk phosphorylation in response to contractile stimuli was muscle-type dependent with greater increases in the plantaris than the soleus. These results suggest that diabetes alters intramuscular signaling processes in response to a contractile stimulus.

Overload Induced Heat Shock Proteins (HSPs), MAPK and miRNA (miR-1 and miR133a) Response in Insulin-Resistant Skeletal Muscle

“…Verification of transfer efficiency and equal loading of protein among lanes was determined by Ponceau S. Immunodetection of antigens was performed as described previously [34,35]. In brief, membranes were blocked for 1 h at room temperature with constant shaking in blocking buffer (5% non-fat dry milk in TBS-T (20mM Tris-base, 150mM NaCl, 0.05% Tween-20), pH 7.6) followed by serial washes in TBS-T at room temperature.…”

Insulin resistance syndrome blunts the mitochondrial anabolic response following resistance exercise

“…ALTHOUGH PHYSICAL ACTIVITY is an effective, low-cost, and nonpharmacological alternative to traditional prevention and treatment methods for insulin resistance syndrome (40,41), insulin-resistant skeletal muscle may be "desensitized" to the anabolic action of exercise (14,37,38,47,51,59,63). Considering the putative role of mitochondria in the development and progression of insulin resistance syndrome (49), the contractile activity-induced response of the organelle in metabolic disease states is of particular interest (34).…”

“…Although augmentations of mitochondrial protein synthesis rates appear to dissipate after the initial RE bout in young individuals (66), older adults exhibit a sustained increase in the translational capacity of mitochondrial proteins even after several months of resistance training (46,61). Despite clinically significant improvements in risk factors associated with insulin resistance syndrome following longterm participation in moderate-intensity resistance exercise (10,12,17,62), several studies indicate that insulin resistance (and/or related comorbidities) may limit gains in muscle mass (51,59) and strength (35) by altering anabolic signaling events following resistance-type contractile activity (37,38,51). Paturi et al (51) recently reported an attenuated hypertrophic response in soleus muscle following synergistic ablation of gastrocnemius and plantaris in the obese Zucker rat (fa/fa), a widely recognized model of genetic obesity and insulin resistance syndrome.…”

Impaired overload-induced hypertrophy is associated with diminished mTOR signaling in insulin-resistant skeletal muscle of the obese Zucker rat

“…Previous data from our laboratory have suggested that the capacity of the OZ soleus muscle to undergo hypertrophy in response to increased loading is diminished compared with that observed in the lean Zucker (LZ) rat. Why metabolic syndrome may affect the hypertrophic response of muscle is not clear although we and others have noted that insulin resistance is associated with differences in the ability of skeletal muscle to activate intracellular signaling cascades in response to alterations in contractile activity (14,19,20,34).…”