Cadmium induces impaired glucose tolerance in rat by down-regulating GLUT4 expression in adipocytes.
Cadmium (Cd) has been known to cause hyperglycemia with diabetes-related complications in experimental animals; however, the molecular basis underlying this Cd-induced hyperglycemia is not known. Here, we report the novel finding that the impaired glucose tolerance (IGT) in rats induced by CdCl(2) is accompanied by a drastic (by as much as 90%) and dose-dependent reduction in GLUT4 protein and GLUT4 mRNA levels in adipocytes. The effect was specific to GLUT4; neither GLUT1 nor insulin-responsive aminopeptidase in adipocytes was affected. GLUT2 in hepatocytes was also not affected. Interestingly, the effect on GLUT4 was also specific to adipocytes; the muscle tissues of the Cd-treated rats showed only a slight (<25%) reduction in GLUT4 protein level with no change in GLUT4 message level, and again with no change in GLUT1 protein and its message levels. Although the insulin-induced GLUT4 translocation in adipocytes was not affected by the Cd treatment, the 3-O-methy-D-glucose flux in insulin-stimulated adipocytes of Cd-treated rat was drastically reduced. Together these findings clearly demonstrate that Cd induces IGT in rats by selectively down-regulating GLUT4 expression in adipocytes.
Han
Jin C
JC
Department of Biochemistry, College of Medicine, Dongguk University, 707 Sukjang-dong, Kyungju, Kyungpook 780-714, South Korea.
Park
Seung Y
SY
Hah
Byoung G
BG
Choi
Geum H
GH
Kim
Yung K
YK
Kwon
Tae H
TH
Kim
Eui K
EK
Lachaal
Moshen
M
Jung
Chan Y
CY
Lee
Wan
W
D019325:3-O-Methylglucose / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006943:Hyperglycemia; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D002104:Cadmium; D019325:3-O-Methylglucose; D005947:Glucose; D019256:Cadmium Chloride