Insulin therapy normalizes GLUT1 glucose transporter mRNA but not immunoreactive transporter protein in streptozocin-diabetic rats.
Previous studies have shown that the principal glucose transporter isoform within the blood-brain barrier (BBB) is GLUT1, and that GLUT1 mRNA is upregulated and immunoreactive GLUT1 protein is downregulated in rats with streptozocin (STZ)-induced experimental diabetes. The present studies investigate effects of insulin therapy on both GLUT1 mRNA and immunoreactive GLUT1 protein in brain capillaries isolated from control (CO), diabetic (DM), and insulin-treated diabetic (IRx) rats. The following variables were measured: serum glucose levels, rat brain capillary immunoreactive GLUT1 level by quantitative Western blotting, and rat brain capillary GLUT1 and actin mRNA levels by quantitative Northern blotting. Serum glucose levels were 6.4 +/- 1.2, 30.3 +/- 3.2, and 3.7 +/- 1.7 mmol/L in CO, DM, and IRx rats, respectively. Brain capillary immunoreactive GLUT1 transporter protein level was 53% +/- 13% of CO values in DM rats, and this value was unchanged with insulin treatment. GLUT1 mRNA level in rat brain was increased to 131% +/- 8% of CO values in DM rats and was 80% +/- 5% of CO values in IRx rats. In conclusion, short-term insulin therapy in rats with STZ-induced diabetes normalizes BBB GLUT1 mRNA level, but does not normalize depressed immunoreactive GLUT1 protein level.
Lutz
A J
AJ
Department of Medicine, Division of Endocrinology, UCLA School of Medicine.
Pardridge
W M
WM
D000199:Actins / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001812:Blood-Brain Barrier; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply; D001923:Brain Chemistry; D002196:Capillaries / Q000737:chemistry / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D007328:Insulin / Q000627:therapeutic use*; D007536:Isomerism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D000199:Actins; D001786:Blood Glucose; D051272:Glucose Transporter Type 1; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D013311:Streptozocin