Abnormal glucose transport and GLUT1 cell-surface content in fibroblasts and skeletal muscle from NIDDM and obese subjects |
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| Authors: | C Miele P Formisano G Condorelli M Caruso F Oriente F Andreozzi C G Tocchetti G Riccardi F Beguinot |
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| Institution: | (1) Department of Cellular and Molecular Biology and Pathology, and C. N. R. Center of Experimental Endocrinology and Oncology, Naples, Italy, IT;(2) Department of Clinical and Experimental Medicine, “Federico II” University of Naples, Naples, Italy, IT |
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| Abstract: | Summary Glucose transport and GLUT1 expression were studied in fibroblasts from 7 lean and 5 obese non-insulin-dependent diabetic
(NIDDM) subjects with at least 2 NIDDM first-degree relatives and from 12 lean and 5 obese non-diabetic subjects with no family
history of diabetes. The obese individuals also had a strong family history of obesity. Fibroblasts from all of the subjects
exhibited no difference in insulin receptor binding, autophosphorylation, and kinase and hexokinase activity. At variance,
basal 2-deoxyglucose (2-DG) uptake and 3H-cytochalasin B binding were 50 % increased in cells from individuals with NIDDM (p < 0.001) and/or obesity (p < 0.01) as compared to the lean non-diabetic subjects. Insulin-dependent (maximally stimulated – basal) 2-DG uptake and cytochalasin
B binding were decreased three-fold in cells from the diabetic and/or obese subjects (p < 0.01). GLUT1 mRNA and total protein levels were comparable in fibroblasts from all the groups. However, basal GLUT1 cell-surface
content was 50 % greater in fibroblasts from the NIDDM and/or obese subjects as compared to the lean non- diabetic individuals
while insulin-dependent GLUT1 recruitment at the cell surface was diminished threefold. Increased basal GLUT1 content in the
plasma membrane was also observed in skeletal muscle of 4 NIDDM and 3 non-diabetic obese individuals (p < 0.05 vs the lean non diabetic subjects). Basal 2-DG uptake in fibroblasts from diabetic/obese individuals and lean control
subjects strongly correlated with the in vivo fasting plasma insulin concentration of the donor. A negative correlation was
demonstrated between the magnitude of insulin-dependent glucose uptake by the fibroblasts and plasma insulin levels in vivo.
We conclude that a primary abnormality in glucose transport and GLUT1 cell-surface content is present in fibroblasts from
NIDDM and obese individuals. The abnormal GLUT1 content is also present in skeletal muscle plasma membranes from NIDDM and
obese individuals. Diabetologia (1997) 40: 421–429]
Received: 9 August 1996 and in final revised form: 11 December 1996 |
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| Keywords: | NIDDM obesity fibroblasts glucose glucose transporter metabolism |
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