Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase.
The drugs troglitazone and metformin are used to reduce the degree of insulin resistance in type 2 diabetes. Both compounds act through different mechanisms which might include opposing effects on the production of adiponectin, an insulin-sensitizer released by adipocytes. This study compared the effects of troglitazone and metformin on adiponectin production by 3T3-L1 adipocytes during 48 h culture. Troglitazone increased adiponectin mRNA and protein expression as well as release, whereas metformin did not affect transcription but reduced protein expression and release. The effect of metformin was also seen with phenformin, and with low-glucose culture, all conditions with a reduced mitochondrial activity and an activated AMP activated protein kinase (AMPK). Addition of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR) also caused a decrease in adiponectin protein expression. These data indicate that metformin and troglitazone exert opposing effects on adiponectin expression and release by differentiated 3T3-L1 adipocytes. The metformin-induced suppression involves an activation of AMP activated protein kinase.
Huypens
Peter
P
Diabetes Research Center, Brussels Free University-VUB, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Quartier
Erik
E
Pipeleers
Daniël
D
Van de Casteele
Mark
M
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002839:Chromans / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D010629:Phenformin / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D052242:Adiponectin; D002839:Chromans; D017077:Culture Media, Conditioned; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D012265:Ribonucleotides; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D010629:Phenformin; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D000077288:Troglitazone; D005947:Glucose