Glucose and streptozotocin stimulate p135 O-glycosylation in pancreatic islets

Biochem Biophys Res Commun. 2000 Jan 7;267(1):26-32. doi: 10.1006/bbrc.1999.1895.

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.

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism
  • Animals
  • Cell Line
  • Cells, Cultured
  • Glucose / pharmacology*
  • Glycoproteins / drug effects
  • Glycoproteins / isolation & purification
  • Glycoproteins / metabolism*
  • Glycosylation / drug effects
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / physiology*
  • Male
  • Molecular Weight
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / chemistry
  • Streptozocin / pharmacology*
  • Uridine Diphosphate N-Acetylglucosamine / metabolism

Substances

  • Glycoproteins
  • Insulin
  • Uridine Diphosphate N-Acetylglucosamine
  • Streptozocin
  • Glucose
  • Acetylglucosamine