title: Elevated SNAP-25 is associated with fatty acid-induced impairment of mouse islet function.
abstract: The role of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in insulin secretion following chronic exposure to non-esterified fatty acids (NEFAs) has not been extensively investigated. Here, we show that synaptosome-associated protein of 25 kDa (SNAP-25) levels were predominantly elevated in the soluble fraction of mouse islets exposed to palmitate. This coincided with an impairment of insulin secretion to glucose and non-glucose secretagogues, consistent with a defect at a distal regulatory step in exocytosis. Removal of palmitate from the media restored both SNAP-25 protein levels and insulin secretion to control levels. We conclude that increased expression of SNAP-25 is associated with NEFA-induced impairment of insulin secretion in mouse islets.
authors.affiliation: Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Vic. 3050, Australia.
authors.forename: Sakeneh
authors.initials: S
authors.lastname: Zraika
authors.forename: Marjorie E
authors.initials: ME
authors.lastname: Dunlop
authors.forename: Joseph
authors.initials: J
authors.lastname: Proietto
authors.forename: Sofianos
authors.initials: S
authors.lastname: Andrikopoulos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D005947:Glucose