Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion

Academic Article

Abstract

  • Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic β-cells normally respond to glucose challenge by rapid insulin release (first phase insulin secretion), there is a loss of this acute response in virtually all of the type 2 diabetes patients with significant fasting hyperglycemia. Our previous studies demonstrated that irreversible intracellular accumulation of a glucose metabolite, protein O-linked N-acetylglucosamine modification (O-GlcNAc), is associated with pancreatic β-cell apoptosis. In the present study, we show that streptozotocin (STZ), a non-competitive chemical blocker of O-GlcNAcase, induces an insulin secretory defect in isolated rat islet cells. In contrast, transgenic mice with down-regulated glucose to glucosamine metabolism in β-cells exhibited an enhanced insulin secretion capacity. Interestingly, the STZ blockade of O-GlcNAcase activity is also associated with a growth hormone secretory defect and impairment of intracellular secretory vesicle trafficking. These results provide evidence for the roles of O-GlcNAc in the insulin secretion and possible involvement of O-GlcNAc in general glucose-regulated hormone secretion pathways. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Liu K; Paterson AJ; Konrad RJ; Parlow AF; Jimi S; Roh M; Chin E; Kudlow JE
  • Start Page

  • 135
  • End Page

  • 146
  • Volume

  • 194
  • Issue

  • 1-2