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

34 Citations (Scopus)

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

Fingerprint

Streptozocin
Growth Hormone
Insulin
Glucose
Medical problems
Type 2 Diabetes Mellitus
Defects
Acetylglucosamine
Secretory Pathway
Glucosamine
Secretory Vesicles
Metabolites
Islets of Langerhans
Metabolism
Hyperglycemia
Transgenic Mice
Rats
Fasting
Genes
hexosaminidase C

Keywords

  • Diabetes mellitus
  • Glucose
  • Insulin
  • Pituitary

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Liu, K., Paterson, A. J., Konrad, R. J., Parlow, A. F., Jimi, S., Roh, M., ... 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

Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion. / Liu, Kan; Paterson, Andrew J.; Konrad, Robert J.; Parlow, A. F.; Jimi, Shiro; Roh, Meejeon; Chin, Edward; Kudlow, Jeffrey E.

In: Molecular and Cellular Endocrinology, Vol. 194, No. 1-2, 30.08.2002, p. 135-146.

Research output: Contribution to journalArticle

Liu, K, Paterson, AJ, Konrad, RJ, Parlow, AF, Jimi, S, Roh, M, Chin, E & Kudlow, JE 2002, 'Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion', Molecular and Cellular Endocrinology, vol. 194, no. 1-2, pp. 135-146. https://doi.org/10.1016/S0303-7207(02)00155-7
Liu, Kan ; Paterson, Andrew J. ; Konrad, Robert J. ; Parlow, A. F. ; Jimi, Shiro ; Roh, Meejeon ; Chin, Edward ; Kudlow, Jeffrey E. / Streptozotocin, an O-GlcNAcase inhibitor, blunts insulin and growth hormone secretion. In: Molecular and Cellular Endocrinology. 2002 ; Vol. 194, No. 1-2. pp. 135-146.
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