GLYCEMIA-LOWERING EFFECT OF COBALT CHLORIDE IN THE DIABETIC RAT - INCREASED GLUT1 MESSENGER-RNA EXPRESSION

We have recently shown that expression of the GLUT1 glucose transporte r isoform is augmented in cells exposed to cobalt chloride [Co(II)], a n agent that stimulates the expression of hyposia-responsive genes (Be hrooz, A., Ismail-Beigi, F., 1997. J. Biol. Chem. 272, 5555-5562.). He re, 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 th e drinking water reduced the glycemia of streptozotocin-induced diabet ic rats by day 3 from 32.3 +/- 2.1 to 21.0 +/- 1.9 mM (non-fasting). C o(II) resulted in no change in serum insulin levels of normal or diabe tic rats. Treatment with 4 mM Co(II) was more effective than 2 mM Co(I I) in reducing the glycemia of diabetic rats, while 6 mM Co(II) was as sociated with severe toxicity. GLUT1 mRNA content increased significan tly in ventricular myocardium, renal cortex, skeletal muscle, cerebrum and liver of normal and diabetic rats treated with 2 mM cobalt chlori de (ranging from 1.3- to 2.9-fold in the different tissues). It is con cluded that: (1) treatment with Co(II) decreases the glycemia of diabe tic rats, and (2) the glycemia-lowering effect of Co(II) is associated with, and may be mediated by, enhanced expression of GLUT1 mRNA. (C) 1997 Elsevier Science Ireland Ltd.