Glycemia-lowering effect of cobalt chloride in the diabetic rat: increased GLUT1 mRNA expression

• Published in: Molecular and cellular endocrinology Vol. 133; no. 2; pp. 151 - 160
• Main Authors: Ybarra, Juan, Behrooz, Alireza, Gabriel, Allen, Koseoglu, Mehmet H, Ismail-Beigi, Faramarz
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 20.10.1997
• Subjects: Animals; Blood Glucose - metabolism; Body Weight - drug effects; Cobalt - pharmacology; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - genetics; Drinking; Gene Expression Regulation - drug effects; Glucagon; Glucose Transporter Type 1; Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA; Insulin; Insulin - blood; Male; Monosaccharide Transport Proteins - genetics; Organ Specificity; Rats; Rats, Sprague-Dawley; RNA, Messenger - analysis; Streptozotocin; Glucagon; Insulin; Streptozotocin; Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(97)00162-7

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.