5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside increases myocardial glucose uptake during reperfusion and induces late pre-conditioning: potential role of AMP-activated protein kinase.
Late pre-conditioning protects against myocardial ischaemic-reperfusion injury. AMP-activated protein kinase (AMPK) is activated by exercise and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). Early pre-conditioning involves AMPK activation and increased myocardial glucose uptake. The aim of the present study was to determine whether AICAR activates myocardial AMPK and induces late pre-conditioning and whether myocardial glucose uptake during reperfusion was modulated. Twenty-four hours after AICAR treatment or exercise, Wistar rats were subjected to ischaemia and reperfusion in a Langendorff model and compared to control rats. AMPK activity increased immediately 2.5-fold in AICAR-treated animals (P < 0.01) and twofold in exercised animals (P < 0.05). AICAR and exercise reduced infarct size by 60% and 50% (both P < 0.01), respectively, and increased myocardial glucose uptake during reperfusion (AICAR; 45%, P < 0.05, exercise; 40%, P < 0.05). In conclusion, AICAR induces late pre-conditioning and increases myocardial glucose uptake during reperfusion in rat hearts. AICAR and exercise activate AMPK, suggesting a role of AMPK in the signalling mechanisms behind late pre-conditioning.
Kristiansen
Steen B
SB
Department of Cardiology, Aarhus University Hospital, Skejby Sygehus, Denmark. sbk@iekf.au.dk
Solskov
Lasse
L
Jessen
Niels
N
Løfgren
Bo
B
Schmitz
Ole
O
Nielsen-Kudsk
Jens Erik
JE
Nielsen
Torsten T
TT
Bøtker
Hans Erik
HE
Lund
Sten
S
D055372:AMP-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000737:chemistry / Q000378:metabolism; D006003:Glycogen / Q000032:analysis; D006321:Heart / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D005082:Physical Exertion / Q000502:physiology; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000378:metabolism / Q000494:pharmacology*; D017725:Ventricular Pressure / Q000187:drug effects
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D020011:Protective Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D006003:Glycogen; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose