Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-α/β, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade.

We investigated the importance of the two catalytic alpha-isoforms of the 5'-AMP-activated protein kinase (AMPK) in 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) and contraction-induced glucose uptake in skeletal muscle. Incubated soleus and EDL muscle from whole-body alpha2- or alpha1-AMPK knockout (KO) and wild type (WT) mice were incubated with 2.0 mm AICAR or electrically stimulated to contraction. Both AICAR and contraction increased 2DG uptake in WT muscles. KO of alpha2, but not alpha1, abolished AICAR-induced glucose uptake, whereas neither KO affected contraction-induced glucose uptake. AICAR and contraction increased alpha2- and alpha1-AMPK activity in wild type (WT) muscles. During AICAR stimulation, the remaining AMPK activity in KO muscles increased to the same level as in WT. During contraction, the remaining AMPK activity in alpha2-KO muscles was elevated by 100% probably explained by a 2-3-fold increase in alpha1-protein. In alpha1-KO muscles, alpha2-AMPK activity increased to similar levels as in WT. Both interventions increased total AMPK activity, as expressed by AMPK-P and ACCbeta-P, in WT muscles. During AICAR stimulation, this was dramatically reduced in alpha2-KO but not in alpha1-KO, whereas during contraction, both measurements were essentially similar to WT in both KO-muscles. The results show that alpha2-AMPK is the main donor of basal and AICAR-stimulated AMPK activity and is responsible for AICAR-induced glucose uptake. In contrast, during contraction, the two alpha-isoforms seem to substitute for each other in terms of activity, which may explain the normal glucose uptake despite the lack of either alpha2- or alpha1-AMPK. Alternatively, neither alpha-isoform of AMPK is involved in contraction-induced muscle glucose uptake.