Effects of altered glucose homeostasis on glucose transporter expression in skeletal muscle of the rat.

Abstract

Previous studies have suggested that alteration in the expression of the insulin-regulatable glucose transporter of muscle (GLUT4 protein) may be an important determinant of insulin action. In the present studies, we have examined GLUT4 mRNA and protein concentrations in muscle after variations in the metabolic status of the intact animal (i.e., 7 d streptozotocin-induced diabetes, 7 d insulin-induced hypoglycemia, and 3 d fasting). These changes in glucose homeostasis were associated with the following changes in GLUT-4 gene products: a decrease of 30% in both mRNA and protein with diabetes; a 50% increase in mRNA and a 2.4-fold increase in protein with insulin injection; and normal mRNA in spite of a 2.7-fold increase in protein with fasting. Fasted diabetics exhibited an increase of 50% in GLUT4 mRNA and a 2.4-fold increase in protein relative to fed diabetics. In diabetic and insulin-injected groups, the changes in GLUT-4 protein were similar to changes in mRNA, but in fasting, GLUT-4 protein increased without a concomitant change in mRNA. Overall there was no correlation between muscle concentrations of GLUT4 protein and mRNA. Muscle GLUT4 protein concentration tended to correlate with plasma glucose (r = -0.57, P < 0.001), but not with plasma insulin. These results indicate that (a) chronic changes in glucose homeostasis are associated with changes in expression of GLUT4 protein in muscle; (b) GLUT-4 protein increased in fasted soleus muscle without change in mRNA, thereby differing from fasted adipocytes in which both GLUT4 products diminish; and (c) no simple relationship exists between total muscle GLUT-4 protein content and whole-body insulin sensitivity. (J. Clin. Invest. 1990. 86:542-547.)

Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle

“…The mechanism by which various muscle fibres respond in such a different manner to diabetes or fasting modifying GLUT-4 gene expression remains to be investigated. Our data, revealing a differential regulation of GLUT-4 expression in red and white muscle, could explain some discrepancies previously reported about the effect of fasting [28,49] or diabetes [24,27,50] in skeletal muscle.…”

“…On the basis of recently published data on the diabetesinduced decrease in GLUT-4 in peripheral tissues [22][23][24][25][26][27][28] and on the differential content of GLUT-4 in red and white muscle [29,30], it has been proposed that the level of GLUT-4 expression influences the insulin effect on glucose transport. Supporting this view, we have observed that, in heart and skeletal muscle from diabetic rats, a fall in GLUT-4 protein content coincides with a decreased effect of insulin stimulating glucose transport [4,[6][7][8].…”

“…Thus, diabetes leads to a marked decrease in GLUT-4 expression in skeletal muscle and adipose tissue by suppression at a pretranslational step [22][23][24][25][26][27][28], paralleling insulin action in consequence. In addition, the greater content of GLUT-libitum and housed in animal quarters maintained at 22°C with a 12 h-light/ 12 h-dark cycle.…”

Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance.

“…Decreased GLUT4 levels are also seen in several animal models of chronic hyperglycemia such as in the streptozotocin treated diabetic rat and the Zucker ZDF/Drt-fa rat (26)(27)(28). Decreased GLUT4 levels such as are seen in these animal models are not observed in human NIDDM where total GLUT4 levels are normal but GLUT4 function or translocation is impaired (29,30).…”

Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients

“…Therefore, impaired suppression of HGO could account for the 29 % reduction in S~ in our diabetic cirrhotic patients. Another possible explanation for the reduction in So is a depletion of tissue glucose transporters, or a reduction in their activity as hyperglycaemia causes a depletion of the insulin-regulated glucose transporter (GLUT 4) in skeletal muscle [33]; thus chronic hyperglycaemia rather than a primary genetic abnormality may be responsible for the lower SG in diabetic patients. The normal So in non-diabetic cirrhotic patients is consistent with this hypothesis.…”