Recent in vitro and in vivo studies suggested that the increased flux of glucose through the hexosamine biosynthetic pathway may contribute to glucoseinduced insulin resistance and to the induction of the synthesis of growth factors. Because glutamine:fructose-6-phosphate amidotransferase (GFAT) catalyzes the first and rate-limiting step in the formation of hexosamine products, this enzyme is the key regulator in this pathway and is therefore possibly also involved in the alterations occurring in preclinical or manifest diabetic patients. To study the expression of GFAT in human tissues, we produced and characterized a peptic antiserum specifically recognizing GFAT protein and a riboprobe for the detection of GFAT mRNA. Immunohistochemical and nonradioactive in situ hybridization analysis revealed high levels of expression of GFAT protein and mRNA in adipocytes and skeletal muscle. Furthermore, a marked GFAT expression was found in vascular smooth muscle cells with unexpectedly high variability and lower levels in other cells, e.g., peripheral nerve sheath cells or endocrine-active cells, including the pancreatic islet cell. GFAT protein expression was below detection level in endothelium, osteocytes, lymphocytes, granulocytes, and in most quiescent fibroblasts. In renal tissue, GFAT was expressed in tubular epithelial cells, while glomerular cells remained essentially unstained. Renal sections obtained from patients with diabetic nephropathy showed significant GFAT expression in some glomerular epithelial and mesangial cells, indicating that GFAT expression may be induced by manifest diabetes. Our data indicate that GFAT is expressed in most tissues involved in the development of diabetic late complications. Furthermore, the results suggest that GFAT gene expression is highly regulated
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Metabolism and Signal Transdution|
February 01 1998
Expression of Glutamine:Fructose-6-Phosphate Amidotransferase in Human Tissues: Evidence for High Variability and Distinct Regulation in Diabetes
Andreas G Nerlich;
Andreas G Nerlich
Department of Pathology, University of Munich, Institute for Diabetes Research
Munich
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Ulrich Sauer;
Ulrich Sauer
Department of Pathology, University of Munich, Institute for Diabetes Research
Munich
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Verena Kolm-Litty;
Verena Kolm-Litty
Division of Endocrinology, Department for Internal Medicine
Metabolism
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Eva Wagner;
Eva Wagner
Division of Endocrinology, Department for Internal Medicine
Metabolism
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Matthias Koch;
Matthias Koch
Pathobiochemistry, University of Tübingen
Tübingen, Germany
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Erwin D Schleicher
Erwin D Schleicher
Pathobiochemistry, University of Tübingen
Tübingen, Germany
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Address correspondence and reprint requests to Dr. Erwin Schleicher, Med. Klinik und Poliklinik IV (Med. Director Dr. H.U. Haring), Otfried-Muller-Str. 10, D-72076 Tubingen, Germany. E-mail: [email protected]
Diabetes 1998;47(2):170–178
Article history
Received:
July 08 1997
Revision Received:
October 22 1997
Accepted:
October 22 1997
PubMed:
9519709
Citation
Andreas G Nerlich, Ulrich Sauer, Verena Kolm-Litty, Eva Wagner, Matthias Koch, Erwin D Schleicher; Expression of Glutamine:Fructose-6-Phosphate Amidotransferase in Human Tissues: Evidence for High Variability and Distinct Regulation in Diabetes. Diabetes 1 February 1998; 47 (2): 170–178. https://doi.org/10.2337/diab.47.2.170
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