Glucose and Streptozotocin Stimulate p135 O-Glycosylation in Pancreatic Islets

Increased O-GlcNAc transferase in pancreas of rats with streptozotocin-induced diabetes

“…Of note STZ-induced accumulation of O-GlcNAc in the beta cells is implicated in beta cell apoptosis. Our study showed that more O-GlcNAcylated proteins, measured in total pancreatic proteins, are present in STZ-diabetic rats than in control rats [55,56] and that the amount of the OGTase is stimulated in STZ-diabetic rats. Thus we think that STZ has effects not only on the islet cells but also on the exocrine cells.…”

“…Our data indicates that OGTase plays a part in the modulation of O-GlcNAc concentrations in the beta cells of STZ-diabetic pancreas. Recently, it was shown that STZ and glucose increase the O-GlcNAcylation of beta-cell proteins, especially 135,000-M r protein [53,55,56]. In the absence of hyperglycaemia, STZ itself does not alter the O-GlcNAcylation in beta cells [56].…”

Targeting O-Glycosyltransferase (OGT) to Promote Healing of Diabetic Skin Wounds

“…Hyperglycemia, excess glucose, feeds into the glucosamine pathway to provide excess UDP-GlcNAc for OGT to modify intracellular proteins (3). Excess glucose is converted to glucosamine, which is ultimately converted to UDP-N-acetylglucosamine (UDP-GlcNAc), the donor substrate for OGT modification of intracellular proteins.…”

“…Excess glucose is converted to glucosamine, which is ultimately converted to UDP-N-acetylglucosamine (UDP-GlcNAc), the donor substrate for OGT modification of intracellular proteins. Consequently, hyperglycemia is associated with increased O-GlcNAc modification of a variety of proteins (3)(4)(5)(6)(7). The increased O-GlcNAc modification of intracellular proteins observed in hyperglycemic states including diabetes is thought to contribute to some of the pathology associated with diabetes.…”

Transient downregulation of protein O-N-acetylglucosaminylation by treatment of high-dose nicotinamide in human cells

“…The decrease in the level of the O-GlcNAcylated proteins showed a time-course profile that is identical to that of Sp1 ( Figure 3B, NAM). Furthermore, the nicotinamide-induced decrease in both the O-GlcNAcylation level of cellular proteins and the Sp1 level was blocked by co-treatment of 10 mM glucosamine, a key precursor and stimulator of protein O-GlcNAcylation (Konrad et al, 2000) or 45 mM 2-deoxyglucose, a glucose-derivative that has been shown to inhibit protein de-GlcNAcylation (Kang et al, 2003) (Figure 3B, NAM + GA and NAM + 2-DG). This strongly suggests a possibility of a direct interference by nicotinamide in protein O-GlcNAcylation.…”