title: Short-term adenosine monophosphate-activated protein kinase activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside treatment increases the sirtuin 1 protein expression in skeletal muscle.
abstract: Adenosine monophosphate-activated protein kinase (AMPK) has been proposed to stimulate mitochondrial biogenesis and fat and glucose metabolism in skeletal muscle. Nicotinamide adenine dinucleotide-dependent histone deacetylase sirtuin 1 (SIRT1) is also thought to play a pivotal role for such metabolic adaptations. The purpose of the present study was to examine the effect of AMPK activation with the administration of AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) to rats on skeletal muscle SIRT1 protein expression as well as peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α) and glucose transporter 4 (GLUT4) protein expression and hexokinase activity. The AICAR promoted the phosphorylation of AMPK α-subunit (Thr¹⁷²) and acetyl-coenzyme A carboxylase (Ser⁷⁹) without any change of total AMPK α-subunit or acetyl-coenzyme A carboxylase protein levels in both the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. The SIRT1 protein expression increased at 24 hours after administration of AICAR in the EDL muscle but not in the soleus muscle. The PGC-1α protein expression increased in both the soleus and EDL muscles and GLUT4 did in the EDL muscle at 24 hours after an administration of AICAR. The hexokinase activity increased at 18 and 24 hours in the soleus and at 12, 18, and 24 hours in the EDL after an AICAR treatment. These results suggest that short-term AICAR treatment to rats promotes skeletal muscle AMPK phosphorylation and then coincidently increases the SIRT1 protein expression. In addition, such treatment also enhances the PGC-1α and GLUT4 protein contents and hexokinase activity in skeletal muscle.
authors.affiliation: Faculty of Life Design, Tohoku Institute of Technology, 6 Futatsusawa, Taihaku-ku, Sendai, Miyagi 982-8588, Japan. suwa-m@tohtech.ac.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Suwa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Radak
authors.forename: Shuzo
authors.initials: S
authors.lastname: Kumagai
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D016601:RNA-Binding Proteins / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology*; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D012265:Ribonucleotides; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; D000620:Aminoimidazole Carboxamide; D006593:Hexokinase; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide