The effects of the glycation of transferrin on chromium binding and the transport and distribution of chromium in vivo.
Chromium (III) has been shown to act as a pharmacological agent improving insulin sensitivity in rodent models of obesity, insulin resistance, and diabetes. To act in beneficial fashion, chromium must reach insulin-sensitive tissues. Chromium is transported from the bloodstream to the tissues by the iron-transport protein transferrin. When blood concentrations of glucose are high (as in a diabetic subject), transferrin can be glycated, modifying its ability to bind and transport iron. However, the effects of glycation of transferrin on its ability to bind and transport Cr have not been examined previously. Storage of transferrin at 37°C in the presence and absence of glucose has significant effects on the binding of Cr. Transferrin stored in the absence of glucose only binds one equivalent of Cr tightly, compared to the normal binding of two equivalents of Cr by transferrin. Glycated transferrin (stored in the presence of glucose) binds two equivalents of Cr but the changes in its extinction coefficient at 245nm that accompany binding suggest that the Cr-bound transferrin possesses a conformation that deviates appreciably from untreated transferrin. These changes have dramatic effects, greatly reducing the ability of transferrin to transport Cr in vivo in rats. The results suggest that glycation of transferrin in subjects with high blood glucose concentrations should reduce the ability of Cr from pharmacological agents to enter tissues.
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487-0336, USA.
Ge
G
Deng
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487-0336, USA.
Samantha L
SL
Dyroff
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487-0336, USA.
Molly
M
Lockart
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487-0336, USA.
Michael K
MK
Bowman
Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487-0336, USA. Electronic address: jvincent@bama.ua.edu.
John B
JB
Vincent
D000818:Animals; D001693:Biological Transport, Active; D002417:Cattle; D002857:Chromium / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy; D006031:Glycosylation; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D014168:Transferrin; D002857:Chromium
Chromium; Distribution; Kinetic; Transferrin; Transport