Impairment of insulin-stimulated GLUT4 translocation in skeletal muscle and adipose tissue in the Tsumura Suzuki obese diabetic mouse: a new genetic animal model of type 2 diabetes.
BACKGROUND
In skeletal muscle and adipocytes, insulin-stimulated glucose transport has been known to occur through the translocation of glucose transporter (GLUT) 4 from the intracellular pool to the plasma membrane. The Tsumura Suzuki obese diabetic (TSOD) mouse, a new genetic animal model of type 2 diabetes, develops moderate degrees of obesity and diabetes that are especially apparent in animals more than 11 weeks old. A defect in insulin stimulation of GLUT4 translocation also contributes to the characteristics of type 2 diabetes.


OBJECTIVE
To characterize this mouse further, we examined the alteration in insulin-stimulated GLUT4 translocation in the skeletal muscle and adipose tissue.


METHODS
For glucose and insulin tolerance tests, the mice were given glucose or insulin and blood samples were collected. After isolation of low-density microsomal membrane and plasma membrane from skeletal muscle and adipose tissue, insulin-stimulated translocation of GLUT4 in these TSOD mice was examined by Western blot.


CONCLUSIONS
TSOD mice showed a significant increase in blood glucose after the glucose load, and exhibited a significantly attenuated decrease in blood glucose concentrations after administration of insulin, compared with that in control Tsumura Suzuki non-obese (TSNO) mice. The insulin-stimulated translocation of GLUT4 from low-density microsomal membranes to plasma membrane was significantly reduced in both skeletal muscle and adipose tissue of TSOD mice. These results indicate that the reduced insulin sensitivity in diabetic TSOD mice is presumably due, at least in part, to the impaired GLUT4 translocation by insulin in both skeletal muscle and adipocytes.
Miura
T
T
Department of Clinical Nutrition, Suzuka University of Medical Science, Faculty of Health Science, 1001-1 Kishioka-cho, Suzuka, Mie 510-0293, Japan. miura@suzuka-u.ac.jp
Suzuki
W
W
Ishihara
E
E
Arai
I
I
Ishida
H
H
Seino
Y
Y
Tanigawa
K
K
D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002462:Cell Membrane / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D008861:Microsomes / Q000648:ultrastructure; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009765:Obesity
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse