Muscle group-specific regulation of GLUT 4 glucose transporters in control, diabetic, and insulin-treated diabetic rats.
Insulin resistance in diabetic rats involves pretranslational suppression of the GLUT 4 glucose transporter in muscle. Because the capacity for insulin-mediated glucose transport varies as a function of muscle group, we hypothesized that GLUT 4 was differentially expressed and regulated by diabetes in a muscle-specific manner. We studied control (C), streptozocin (STZ)-induced diabetic (D), and insulin-treated diabetic (Tx) rats and examined the following muscles that vary in fiber composition: soleus (type I fibers), gastrocnemius (mixed type IIa > IIb), vastus lateralis and rectus abdominis (type IIb > IIa), and cardiac muscle. In C animals, these muscles exhibited significant differences in the baseline expression of GLUT 4. Relative GLUT 4 content was highest in cardiac muscle, intermediate in soleus, and significantly lower in gastrocnemius, rectus abdominis, and vastus lateralis (1.8:1.0:0.6). The impact of diabetes and insulin therapy on GLUT 4 expression also varied as a function of muscle group. After four weeks of diabetes, GLUT 4 levels were reduced by approximately 50% in cardiac muscle, soleus, and gastrocnemius. In contrast, GLUT 4 content in rectus abdominis and vastus lateralis was similar to that in control rats. Exogenous insulin treatment of diabetic rats increased GLUT 4 content in soleus, cardiac muscle, and gastrocnemius, but had no effect in either vastus lateralis or rectus abdominis. Temporal effects of diabetes and insulin treatment were also examined in different skeletal muscle. Soleus showed a significant decrease in GLUT 4 content as early as 2 days with a further decrease at 4 weeks; rectus abdominis showed little change at either time point.(ABSTRACT TRUNCATED AT 250 WORDS)
Hardin
D S
DS
Section of Endocrinology, Indianapolis Veterans Administration Medical Center, IN.
Dominguez
J H
JH
Garvey
W T
WT
D000704:Analysis of Variance; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D051275:Glucose Transporter Type 4; D015151:Immunoblotting; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D013311:Streptozocin