The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells.
Increased production of inflammatory cytokines is suggested to be of importance for initiation and progression of insulin resistance. Chronic treatment with the AMP analogue 5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleoside (AICAR) has been shown to improve insulin sensitivity and prevent the development of diabetes in rodents. We investigated the effects of AICAR on the expression and production of inflammatory cytokines from human adipose tissue and skeletal muscle cells as well as intact rat skeletal muscles in vitro. AICAR dose-dependently decreased interleukin-6 (IL-6) gene expression and secretion in human adipose tissue and in human skeletal muscle cells. In parallel, AICAR inhibited interleukin-8 (IL-8) secretion in human adipose tissue and skeletal muscle cells, as well as reduced IL-8 gene expression in skeletal muscle cells. In intact rat extensor digitorum longus (EDL) muscle fibres AICAR markedly decreased IL-6 and IL-8 gene expression. In conclusion, AICAR inhibits the production of IL-6 and IL-8 human adipose tissue and in skeletal muscle cells. We suggest that decreased cytokine production might play a role for the AICAR-induced increase in insulin sensitivity.
Lihn
Aina S
AS
Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Sygehus, 8000 Aarhus C, Denmark. lihn@dadlnet.dk
Pedersen
Steen B
SB
Lund
Sten
S
Richelsen
Bjørn
B
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology*; D013997:Time Factors
D052242:Adiponectin; D020536:Enzyme Activators; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide