Metformin ameliorates diabetes but does not normalize the decreased GLUT 4 content in skeletal muscle of obese (fa/fa) Zucker rats. 1993

A Handberg, and L Kayser, and P E Høyer, and M Voldstedlund, and H P Hansen, and J Vinten
Institute of Medical Physiology B, Panum Institute, University of Copenhagen, Denmark.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008687 Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289) Dimethylguanylguanidine,Dimethylbiguanidine,Glucophage,Metformin HCl,Metformin Hydrochloride,HCl, Metformin,Hydrochloride, Metformin
D009004 Monosaccharide Transport Proteins A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES. Hexose Transport Proteins,Band 4.5 Preactin,Erythrocyte Band 4.5 Protein,Glucose Transport-Inducing Protein,Hexose Transporter,4.5 Preactin, Band,Glucose Transport Inducing Protein,Preactin, Band 4.5,Proteins, Monosaccharide Transport,Transport Proteins, Hexose,Transport Proteins, Monosaccharide,Transport-Inducing Protein, Glucose
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D011924 Rats, Zucker Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene. Zucker Rat,Zucker Rats,Rat, Zucker
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003920 Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D003922 Diabetes Mellitus, Type 1 A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence. Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus

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