Vanadate treatment of streptozotocin diabetic rats restores expression of the insulin-responsive glucose transporter in skeletal muscle.
Streptozotocin-treated rats were diabetic, as assessed by blood glucose and plasma insulin values, while vanadate treatment restored blood glucose values to normal. Immunoblot analysis using a monoclonal antibody to the insulin-responsive glucose transporter demonstrated a 70% decline in transporter expression in skeletal muscle of diabetic rats. Subsequent treatment of diabetic animals with vanadate resulted in renewed expression of the transporter to 87% of control levels. Northern blot analysis of total skeletal muscle RNA from diabetic animals revealed a 55% decline in the steady state level of muscle glucose transporter mRNA, while vanadate treatment led to a 187% increase in transporter mRNA over normal levels. These results support the conclusion that vanadate acts to relieve diabetic hyperglycemia by inducing expression of the insulin-responsive glucose transporter at the pretranslational level.
Department of Biochemical Endocrinology, Merck, Sharp, and Dohme Research Laboratories, Rahway, New Jersey 07065.
H V
HV
Strout
P P
PP
Vicario
C
C
Biswas
R
R
Saperstein
E J
EJ
Brady
P F
PF
Pilch
J
J
Berger
D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D007332:Insulin Infusion Systems; D008297:Male; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014638:Vanadates / Q000494:pharmacology* / Q000627:therapeutic use
D015342:DNA Probes; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D014638:Vanadates