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

Kan Liu, Andrew J. Paterson, Robert J. Konrad, A. F. Parlow, Shiro Jimi, Meejeon Roh, Edward Chin, Jeffrey E. Kudlow

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume194
Issue number1-2
DOIs
StatePublished - Aug 30 2002

Keywords

  • Diabetes mellitus
  • Glucose
  • Insulin
  • Pituitary

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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    Liu, K., Paterson, A. J., Konrad, R. J., Parlow, A. F., Jimi, S., Roh, M., Chin, E., & Kudlow, J. E. (2002). Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion. Molecular and Cellular Endocrinology, 194(1-2), 135-146. https://doi.org/10.1016/S0303-7207(02)00155-7