Shortening of poly (A) tail of glucose transporter--one mRNA in experimental diabetes mellitus.
To determine the molecular mechanisms of diabetes-related changes in the expression of GLUT-1 in cerebral tissue, streptozotocin-induced diabetic rats and vehicle injected controls were studied after 4 weeks of diabetes. The GLUT-1 mass in cerebral microvessels was reduced in diabetic rats by approximately 38% (P < 0.01). The GLUT-1 concentration in insulin-treated diabetic group was not significantly different from controls. The GLUT-1 mRNA content of cerebral tissue in diabetic rats (0.064 +/- 0.007) was significantly reduced compared to control rats (0.122 +/- 0.011) or insulin-treated diabetic rats (0.122 +/- 0.015) P < 0.01. The in vitro translation of GLUT-1 mRNA of diabetic rats (0.793 +/- 0.047 arbitrary units) was also significantly lower than that in control rats (1.403 +/- 0.153) P < 0.01 or insulin-treated diabetic rats. (1.124 +/- 0.083) P < 0.01. These changes occurred in asssociation with a reduction in poly (A) tail length of GLUT-1 mRNA which decreased from a control value of 200-350 nt to only 50-100 nt in diabetic rats. Shortening of poly (A) tail of mRNAs is a novel mechanism of diabetes-related changes in the expression of specific genes which are regulated at a translational level.
Shah
G N
GN
Department of Internal Medicine, St. Louis University School of Medicine, MO 63104, USA.
Giddings
S J
SJ
Mooradian
A D
AD
D000818:Animals; D001483:Base Sequence; D002560:Cerebrovascular Circulation; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis*; D011061:Poly A / Q000032:analysis*; D016133:Polymerase Chain Reaction; D016548:Prosencephalon / Q000098:blood supply*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D015183:Restriction Mapping
D017931:DNA Primers; D051272:Glucose Transporter Type 1; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D011061:Poly A