Glycemia-lowering effect of cobalt chloride in the diabetic rat: increased GLUT1 mRNA expression.
We have recently shown that expression of the GLUT1 glucose transporter isoform is augmented in cells exposed to cobalt chloride [Co(II)], an agent that stimulates the expression of hypoxia-responsive genes (Behrooz, A., Ismail-Beigi, F., 1997. J. Biol. Chem. 272, 5555-5562.). Here, we examine the effect of Co(II) on glycemia and tissue GLUT1 mRNA content of normal and diabetic rats. The addition of 2 mM Co(II) in the drinking water reduced the glycemia of streptozotocin-induced diabetic rats by day 3 from 32.3 +/- 2.1 to 21.0 +/- 1.9 mM (non-fasting). Co(II) resulted in no change in serum insulin levels of normal or diabetic rats. Treatment with 4 mM Co(II) was more effective than 2 mM Co(II) in reducing the glycemia of diabetic rats, while 6 mM Co(II) was associated with severe toxicity. GLUT1 mRNA content increased significantly in ventricular myocardium, renal cortex, skeletal muscle, cerebrum and liver of normal and diabetic rats treated with 2 mM cobalt chloride (ranging from 1.3- to 2.9-fold in the different tissues). It is concluded that: (1) treatment with Co(II) decreases the glycemia of diabetic rats, and (2) the glycemia-lowering effect of Co(II) is associated with, and may be mediated by, enhanced expression of GLUT1 mRNA.
Ybarra
J
J
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106-4951, USA.
Behrooz
A
A
Gabriel
A
A
Koseoglu
M H
MH
Ismail-Beigi
F
F
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics*; D004326:Drinking; D005786:Gene Expression Regulation / Q000187:drug effects*; D051272:Glucose Transporter Type 1; D007328:Insulin / Q000097:blood; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D003035:Cobalt; C018021:cobaltous chloride