This study was designed to determine the histological and metabolic effects of the administration of 5'-AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) for 14 successive days. AICAR treatment caused a significant decrease in the percentage of type IIB fibers and the concomitant increase in the percentage of type IIX fibers in extensor digitorum longus (EDL) muscle. The capillary density and the capillary-to-fiber ratio were not altered by AICAR. AICAR treatment increased the glycolytic and oxidative enzyme activities but not the antioxidant enzyme activities. The AICAR treatment increased the uncoupling protein 3 (UCP3) level in EDL and the peroxisome proliferator-activated receptor-gamma coactivator-1alpha protein level in the soleus and EDL muscles, whereas the myogenin level was not altered by AICAR. These results seem to imply that the chronic activation of AMPK alters such muscle histochemical and metabolic characteristics.

AMP-activated protein kinase (AMPK), which was activated by an antihyperglycemic drug metformin, has been hypothesized to mediate metabolic adaptations. The purposes of the present study were 1) to confirm whether acute metformin administration induced AMPK phosphorylation and 2) to determine whether chronic metformin treatment increased the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression, glycolytic and oxidative enzyme activities, and cytochrome c and glucose transporter-4 (GLUT4) protein expressions in the rat soleus and red and white gastrocnemius muscles. The single oral administration of metformin (300 mg/kg body wt) enhanced the AMPK phosphorylation at 5 and/or 6 h after treatment. In the chronic study, rats were fed either normal chow or chow containing 1% metformin for 14 days. Metformin treatment resulted in a mean daily metformin intake of 631 mg.kg body wt(-1).day(-1). Metformin increased the PGC-1alpha content in all three muscles. Metformin increased the hexokinase activity in the white gastrocnemius, the citrate synthase activity in all three muscles, and the beta-hydroxyacyl-CoA dehydrogenase activity in the soleus. The cytochrome c protein content in the soleus muscle also increased. The GLUT4 content was unchanged by metformin. These results suggest that metformin enhances the PGC-1alpha expression and mitochondrial biogenesis possibly at least in part via AMPK phosphorylation in the skeletal muscle. Metformin has thus been proposed to possibly ameliorate insulin resistance, at least partially, by means of such metabolic effects.

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BackgroundToe flexor muscles play an important role in posture and locomotion, and poor toe flexor strength is a risk factor for falls. In this cross-sectional study, we estimated the age-related change in toe flexor strength and compared it with that of handgrip strength. Independent factors predicting toe flexor and handgrip strength were also determined.MethodsA total of 1401 male (aged 35–59 years) study participants were divided into five groups according to their chronological age; 35–39, 40–44, 45–49, 50–54, and 55–59 years. Toe flexor and handgrip strength, anthropometry, and resting blood pressure were measured. Fasting blood samples were collected to measure blood glucose, triglycerides, high- and low-density lipoprotein-cholesterols, and albumin. A self-administered lifestyle questionnaire was conducted.ResultsDecline in absolute toe flexor and handgrip strength began in the age groups 50–55 and 55–59 years, respectively. In comparison to the mean values of the youngest group, relative toe flexor strength (87.0 ± 26.6%) was significantly lower than handgrip strength (94.4 ± 13.1%) for the oldest group. Multiple regression analyses showed that independent factors predicting both toe flexor and handgrip strength were lean body mass, age, serum albumin, drinking habit, and fat mass. Additionally, fasting blood glucose, diastolic blood pressure, sleeping time and exercise habit were predicting factors of toe flexor strength but not of handgrip strength.ConclusionsAge-related reduction in toe flexor strength was earlier and greater than handgrip strength, and toe flexor strength reflects body composition and metabolic status.

The extent to which muscle fiber composition was determined by genes transmitted from parents and the correlated response of the synergistic muscle were analysed by using successive selection of rats. The foundation population (G0) was prepared by random choice from heterogeneous stock produced by random mating of three strains, Wistar-Imamichi, Fischer 344, and Donryu. Selective mating for a high percentage of fast-twitch fibers (%FT) in the deep portion of the lateral head of the gastrocnemius muscle and random mating were made from G0 to the seventh generation (G7). Successive selection caused a significant increase (P < 0.05) of %FT in the gastrocnemius muscle. The realized heritability for seven generations was 0.29. %FT in the soleus muscle of the selected line also increased (P < 0.05). In addition, significantly positive correlations (P < 0.05) were found between %FT in the gastrocnemius and soleus muscles in G1-G7. We conclude that approximately 29% of the variation of %FT was determined by genes transmitted from parents, and %FT in the gastrocnemius muscle was positively correlated with that of the soleus muscle.