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

Authors: Liu, K  Paterson, AJ  Konrad, RJ  Parlow, AF  Jimi, S  Roh, M  Chin E, JR  Kudlow, JE 
Citation: Liu K, etal., Mol Cell Endocrinol 2002 Aug 30;194(1-2):135-46.
Pubmed: (View Article at PubMed) PMID:12242036

Type 2 diabetes mellitus results from a complex interaction between nutritional excess and multiple genes. Whereas pancreatic beta-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 beta-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 beta-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.

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CRRD Object Information
CRRD ID: 1299304
Created: 2004-06-01
Species: All species
Last Modified: 2004-06-01
Status: ACTIVE



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