Effects of metformin and oleic acid on adipocyte expression of resistin.
OBJECTIVE
The adipocyte-secreted hormone resistin has been implicated in obesity-induced insulin resistance and type 2 diabetes, but pharmacological and dietary factors that regulate resistin gene expression and the effects of resistin on cellular glucose uptake in muscle have not been clearly defined.


METHODS
Expression of resistin mRNA was studied in differentiated 3T3-L1 adipocytes by using real-time semiquantitative reverse transcription-polymerase chain reaction. The effects of resistin on insulin-stimulated and insulin-independent 2-deoxyglucose uptake were evaluated in L6 muscle cells.


RESULTS
Insulin 1 microm and rosiglitazone 10 microm markedly reduced resistin mRNA expression (relative to the control gene TF2D) by 4.7-fold (p < 0.05) and 5.3-fold (p < 0.02), respectively. Similar reductions in resistin mRNA were demonstrated with metformin 100 microm (6.2-fold reduction, p < 0.02) and oleic acid 100 microm (3.9-fold reduction, p < 0.03). Resistin 1 microm significantly reduced maximum insulin-stimulated 2-deoxyglucose uptake in L6 cells from 634 to 383% (relative to 100% for control, p < 0.001), and co-administration of rosiglitazone had no effect on resistin-induced insulin resistance. In the absence of insulin, however, resistin increased glucose uptake dose-dependently (e.g., 1.75-fold at 5 microm, p < 0.001) via a mitogen-activated protein kinase-dependent pathway.


CONCLUSIONS
These results demonstrate that various glucose-lowering therapies and oleic acid reduce resistin gene expression in isolated adipocytes, and that resistin impairs insulin-stimulated glucose uptake in skeletal muscle-derived cells.
Rea
R
R
Centre for Integrated Systems Biology and Medicine, School of Medical and Surgical Sciences, University of Nottingham, UK.
Donnelly
R
R
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000737:chemistry / Q000187:drug effects*; D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology; D019301:Oleic Acid / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D052243:Resistin / Q000032:analysis* / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
D000963:Antimetabolites; D007004:Hypoglycemic Agents; D007328:Insulin; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D052243:Resistin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019301:Oleic Acid; D008687:Metformin; D003847:Deoxyglucose