Akt2 is essential for the full effect of calorie restriction on insulin-stimulated glucose uptake in skeletal muscle.
Brief calorie restriction (CR; 20 days of 60% of ad libitum [AL] intake) improves insulin-stimulated glucose transport, concomitant with enhanced phosphorylation of Akt2. The purpose of this study was to determine whether Akt2 is essential for the calorie restriction-induced enhancement in skeletal muscle insulin sensitivity. We measured insulin-stimulated 2-deoxyglucose (2DG) uptake in isolated extensor digitorum longus (EDL) and soleus muscles from male and female wild-type (WT) and Akt2-null (knockout [KO]) mice after ad libitum or calorie-restricted (20 days at 60% of AL) feeding. In WT mice, calorie restriction significantly enhanced insulin-stimulated 2DG uptake in both muscles regardless of sex. However, in KO mice, calorie restriction did not enhance insulin-stimulated 2DG in male or female EDL or in female soleus. Only in male KO soleus did calorie restriction significantly increase insulin-stimulated 2DG through an Akt2-independent mechanism, although 2DG uptake of the KO-CR group was reduced compared with the WT-CR soleus group. Akt2 serine phosphorylation was enhanced approximately two- to threefold in insulin-stimulated WT-CR versus WT-AL muscles. Calorie restriction induced an approximately 1.5- to 2-fold elevation in Akt1 phosphorylation of insulin-treated muscles, regardless of genotype, but this increase was insufficient to replace Akt2 for insulin-stimulated 2DG in Akt2-deficient muscles. These results indicate that Akt2 is essential for the full effect of brief calorie restriction on insulin-stimulated glucose uptake in skeletal muscle with physiologic insulin.
McCurdy
Carrie E
CE
Department of Nutritional Sciences, University of Wisconsin-Madison, USA.
Cartee
Gregory D
GD
D000273:Adipose Tissue / Q000033:anatomy & histology; D000818:Animals; D001835:Body Weight; D004038:Diet, Reducing; D002149:Energy Intake; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt
D007328:Insulin; D011518:Proto-Oncogene Proteins; C494922:Akt2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose