Metformin ameliorates diabetes but does not normalize the decreased GLUT 4 content in skeletal muscle of obese (fa/fa) Zucker rats.
We studied the expression of the glucose transporter GLUT 4 in the soleus and red gastrocnemius muscles from obese, diabetic (fa/fa) Zucker rats compared to their lean littermates (Fa/-), with and without treatment with the antidiabetic drug metformin. In the untreated groups of rats, the GLUT 4 content in a crude membrane fraction of both the soleus and the red gastrocnemius muscles were significantly lower in the obese (fa/fa) rats (3.46 +/- 0.28 vs. 6.04 +/- 0.41, p < 0.001 and 6.0 +/- 0.24 vs. 9.1 +/- 0.48, p < 0.0001, respectively). Differences in GLUT 4 expression in soleus muscle from the same rats were confirmed by quantitative immunofluorescence microscopy, and the results were significantly correlated with the results obtained from quantitative immunoblotting (rho = 0.70, p < 0.0005). The decreased expression of GLUT 4 in fa/fa rats could contribute to the well-established insulin resistance in skeletal muscle of these animals. After 4 weeks of treatment with metformin, weight gain was not affected in either the diabetic (fa/fa) rats or the lean (Fa/-) rats. Improvement of glucose homeostasis by metformin was not associated with normalization of the GLUT 4 expression in the skeletal muscles studied, indicating (1) that the decreased GLUT 4 expression is not directly related to hyperinsulinaemia and diabetes mellitus and (2) that metformin does not normalize the expression of GLUT 4 in skeletal muscle of the diabetic (fa/fa) Zucker rats.
Handberg
A
A
Institute of Medical Physiology B, Panum Institute, University of Copenhagen, Denmark.
Kayser
L
L
Høyer
P E
PE
Voldstedlund
M
M
Hansen
H P
HP
Vinten
J
J
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D019270:Fructosamine; D006595:Hexosamines / Q000097:blood; D015151:Immunoblotting; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity; D051381:Rats; D011924:Rats, Zucker
D015415:Biomarkers; D001786:Blood Glucose; D006595:Hexosamines; D009004:Monosaccharide Transport Proteins; D019270:Fructosamine; D008687:Metformin