Glucose and streptozotocin stimulate p135 O-glycosylation in pancreatic islets.
Streptozotocin has been widely used to create animal models of diabetes. Structurally, streptozotocin resembles N-acetylglucosamine, with a nitrosourea group corresponding to the acetate present in N-acetylglucosamine. Streptozotocin has recently been shown to inhibit O-GlcNAc-selective N-acetyl-beta-d-glucosaminidase, which removes O-linked N-acetylglucosamine from proteins. Compared to other cells, beta-cells express much more of the enzyme O-GlcNAc transferase, which catalyzes addition of O-linked N-acetylglucosamine to proteins. This suggests why beta-cells might be particularly sensitive to streptozotocin. In this report, we demonstrate that both streptozotocin and glucose stimulate O-glycosylation of a 135 kD beta-cell protein. Only the effect of glucose, however, was blocked by inhibition of fructose-6-phosphate amidotransferase, suggesting that glucose acts through the glucosamine pathway to provide UDP-N-acetylglucosamine for p135 O-glycosylation. The fact that both glucose and streptozotocin stimulate p135 O-glycosylation provides a possible mechanism by which hyperglycemia may cause streptozotocin-like effects in beta-cells and thus contribute to the development of type 2 diabetes.
Konrad
R J
RJ
Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, 35233, USA. rkonrad@path.uab.edu
Janowski
K M
KM
Kudlow
J E
JE
D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D006023:Glycoproteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000737:chemistry / Q000494:pharmacology*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
D006023:Glycoproteins; D007328:Insulin; D014537:Uridine Diphosphate N-Acetylglucosamine; D013311:Streptozocin; D005947:Glucose; D000117:Acetylglucosamine