AMPK is indispensable for overload-induced muscle glucose uptake and glycogenesis but dispensable for inducing hypertrophy in mice

Chronic muscle loading (overload) induces skeletal muscles to undergo hypertrophy and to increase glucose uptake. Although AMP-activated protein kinase (AMPK) reportedly serves as a negative regulator of hypertrophy and a positive regulator of glucose uptake, its role in overload-induced skeletal muscle hypertrophy and glucose uptake is unclear. This study aimed to determine whether AMPK regulates overload-induced hypertrophy and glucose uptake in skeletal muscles. To this end, skeletal muscle overload was induced through unilateral synergist ablations in wild-type (WT) and transgenic mice, expressing the dominant-negative mutation of AMPK (AMPK-DN). After 14 days, parameters, including muscle fiber cross-sectional area (CSA), glycogen level, and in vivo [3 H]-2-deoxy-D-glucose uptake, were assessed. No significant difference was observed in body weight or blood glucose level between the WT and AMPK-DN mice. However, the 14-day muscle overload activated the AMPK pathway in WT mice skeletal muscle, whereas this response was impaired in the AMPK-DN mice. Despite a normal CSA gain in each fiber type, the AMPK-DN mice demonstrated a significant impairment of overload-induced muscle glucose uptake and glycogenesis, compared to WT mice. Moreover, 14-day overload-induced changes in GLUT4 and HKII expression levels were reduced in AMPK-DN mice, compared to WT mice. This study demonstrated that AMPK activation is indispensable for overload-induced muscle glucose uptake and glycogenesis; however, it is dispensable for the induction of hypertrophy in AMPK-DN mice. Furthermore, the AMPK/GLUT4 and HKII axes may regulate overload-induced muscle glucose uptake and glycogenesis

PO-245 Exercise at the lactate threshold (LT) and above the LT increases phosphorylation of AMPK and Akt in rat skeletal muscle

  Objective A single bout of exercise can enhance glucose uptake in skeletal muscle. It is well established that AMP-activated protein kinase (AMPK) activation is required for stimulation of glucose uptake by exercise. After the initial phosphorylation of glucose by hexokinase, glucose is further utilized to mitochondrial oxidation during exercise. The direct or functional interaction between hexokinase and Akt may act to integrate glucose metabolism in working muscle. Hence, AMPK and Akt activation would be cooperatively regulated exercise-induced activation of glucose metabolism. Although exercise at the lactate threshold (LT) and above the LT sharply increase glucose uptake via increasing AMPK activity, whether LT exercise can also increase Akt activity is still unknown. Therefore, we examined the AMPK and Akt activity immediately after several intensities of exercise. Methods Male wistar rats (250-270 g) were randomly assigned to 3 groups: Resting control (sedentary, n=16), Low-intensity exercise (LIE: 10 m/min for 30 min, n=8), LT intensity exercise 1 (LTE1: 17.5 m/min for 30 min, n=8), LT intensity exercise 2 (LTE2: 22.5 m/min for 30 min, n=8), and High-intensity exercise (HE: 27.5 m/min for 30 min, n=8). Immediately after each treadmill exercise, plantaris and soleus muscles were dissected. Results LIE exercise did not changed AMPK phosphorylation site (Thr172), indicator of AMPK activity, and Akt phosphorylation site (Ser473, Thr308), indicator of Akt activity, in these muscles compared with resting control. At and above LTE1 exercise increased the phosphorylation of AMPK in these tissues. At and above LTE2 exercise increased the phosphorylation of Akt in these tissues. Therefore, increasing AMPK and Akt activity immediately after LT exercise possibly involved with regulating glucose metabolism. Conclusions Phosphorylation of AMPK and Akt is increased immediately after at and above LT exercise in rat soleus and plantaris muscle. &nbsp

Acute bout of exercise downregulates thioredoxin-interacting protein expression in rat contracting skeletal muscles

We previously reported that in rat skeletal muscle, disuse (i.e., decreased muscle contractile activity) rapidly increases thioredoxin-interacting protein (TXNIP), which is implicated in the reduced glucose uptake. Accordingly, we sought herein to (a) determine the effect of exercise (i.e., increased muscle contractile activity) on muscle TXNIP protein expression, and (b) elucidate the mechanisms underlying the changes of TXNIP protein expression in response to exercise. Rat epitrochlearis and soleus muscles were dissected out after an acute bout of 3-hr swimming (without weight loading) or 3-hr treadmill running (15% grade at 9m/min). In a separate protocol, the isolated epitrochlearis and soleus muscles were incubated for 3 hr with AMP-dependent protein kinase activator AICAR. Immediately after the cessation of the 3-hr swimming, the TXNIP protein was decreased in epitrochlearis but not in soleus muscle. Conversely, 3-hr treadmill running decreased the TXNIP protein in soleus but not in epitrochlearis muscle. TXNIP protein was decreased concomitantly with reduced postexercise muscle glycogen, showing that a decrease in TXNIP protein expression occurs in muscles that are recruited during exercise. In addition, 3-hr incubation with AICAR decreased TXNIP protein in both isolated epitrochlearis and soleus muscles. Our results suggest that (a) an acute bout of exercise downregulates TXNIP protein expression in rat contracting skeletal muscles, and (b) the reduction in TXNIP protein expression in contracting muscles is probably mediated by AMPK activation, at least in part

Egg White Protein Feeding Facilitates Skeletal Muscle Gain in Young Rats with/without Clenbuterol Treatment

Based on the Digestible Indispensable Amino Acid Score (DIAAS), egg white protein (EGG) has an excellent score, comparable to that of whey protein but with a lower amount of leucine. We examined the effect of EGG feeding on rat skeletal muscle gain in comparison to that of two common animal-derived protein sources: casein (CAS) and whey (WHE). To explore the full potential of EGG, this was examined in clenbuterol-treated young rats. Furthermore, we focused on leucine-associated anabolic signaling in response to EGG after single-dose ingestion and chronic ingestion, as well as clenbuterol treatment. Because EGG is an arginine-rich protein source, a portion of the experiment was repeated with diets containing equal amounts of arginine. We demonstrated that EGG feeding accelerates skeletal muscle gain under anabolism-dominant conditions more efficiently than CAS and WHE and this stronger effect with EGG is not dependent on the arginine-rich composition of the protein source. We also demonstrated that the plausible mechanism of the stronger muscle-gain effect with EGG is not detectable in the mechanistic target of rapamycin (mTOR) or insulin signaling under our experimental conditions. We conclude that EGG may have a superior efficiency in muscle gain compared to other common animal-based proteins