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Glucose and streptozotocin stimulate p135 O-glycosylation in pancreatic islets

Authors :
Karen M. Janowski
Jeffrey E. Kudlow
Robert J. Konrad
Source :
Biochemical and biophysical research communications. 267(1)
Publication Year :
2000

Abstract

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.

Details

ISSN :
0006291X
Volume :
267
Issue :
1
Database :
OpenAIRE
Journal :
Biochemical and biophysical research communications
Accession number :
edsair.doi.dedup.....f245dbb3950fe120f9fa386c3b20991b