Transferrin and iron induce insulin resistance of glucose transport in adipocytes.
Normal serum can increase the rate of lipolysis in isolated adipocytes. Recently, we reported that the lipolytic effect of serum could be partly explained by effects of iron and transferrin. To further investigate these effects on fat cell metabolism, we have investigated effects of serum, iron, and transferrin on glucose transport in isolated rat adipocytes. Adipocytes were isolated by collagenase digestion of rat epididymal fat pads, and glucose transport was measured as uptake of [3H]2-deoxyglucose, measured in the presence of 0 to 25 ng/mL insulin. Insulin stimulated glucose transport approximately 8- to 10-fold, with a half-maximally effective concentration (EC50) of approximately 0.15 ng/mL. This was not affected by 45-minute treatment with normal human serum. However, when adipocytes were incubated with serum for 4 hours, cells became markedly insulin resistant. This was manifested as decrease in maximally stimulated glucose transport and a rightward shift in the dose-response curve. Both FeS04 (3 microg/mL) and transferrin (100 microg/mL) had similar, although less pronounced effects on insulin-stimulated glucose transport. Treatment of adipocytes with palmitic acid (120 micromol/L), representing the concentration of fatty acids released into the media after 4 hours of serum treatment, did not alter the effect of insulin on glucose transport. We conclude that transferrin and iron induce insulin resistance of glucose transport in adipocytes through a mechanism independent of fatty acids. These findings may further explain the association between body iron stores and risk of type 2 diabetes mellitus.
Green
Allan
A
Bassett Research Institute, Bassett Healthcare, Cooperstown, NY 13326, USA. allan.green@bassett.org
Basile
Robin
R
Rumberger
John M
JM
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002469:Cell Separation; D016895:Culture Media, Serum-Free; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology*; D007501:Iron / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000494:pharmacology*
D016895:Culture Media, Serum-Free; D005230:Fatty Acids, Nonesterified; D014168:Transferrin; D003847:Deoxyglucose; D007501:Iron; D005947:Glucose