title: A role for SPARC in the moderation of human insulin secretion.
abstract: OBJECTIVE
  We have previously shown the implication of the multifunctional protein SPARC (Secreted protein acidic and rich in cysteine)/osteonectin in insulin resistance but potential effects on beta-cell function have not been assessed. We therefore aimed to characterise the effect of SPARC on beta-cell function and features of diabetes.
  
  
  METHODS
  We measured SPARC expression by qRT-PCR in human primary pancreatic islets, adipose tissue, liver and muscle. We then examined the relation of SPARC with glucose stimulated insulin secretion (GSIS) in primary human islets and the effect of SPARC overexpression on GSIS in beta cell lines.
  
  
  RESULTS
  SPARC was expressed at measurable levels in human islets, adipose tissue, liver and skeletal muscle, and demonstrated reduced expression in primary islets from subjects with diabetes compared with controls (p< = 0.05). SPARC levels were positively correlated with GSIS in islets from control donors (p< = 0.01). Overexpression of SPARC in cultured beta-cells resulted in a 2.4-fold increase in insulin secretion in high glucose conditions (p< = 0.01).
  
  
  CONCLUSIONS
  Our data suggest that levels of SPARC are reduced in islets from donors with diabetes and that it has a role in insulin secretion, an effect which appears independent of SPARC's modulation of obesity-induced insulin resistance in adipose tissue.
authors.affiliation: Institute of Biomedical and Clinical Sciences, Exeter Medical School, University of Exeter, Exeter, United Kingdom. L.W.Harries@exeter.ac.uk
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
authors.forename: Laura J
authors.initials: LJ
authors.lastname: McCulloch
authors.forename: Janet E
authors.initials: JE
authors.lastname: Holley
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rawling
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Welters
authors.forename: Katarina
authors.initials: K
authors.lastname: Kos
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D015676:Osteonectin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007328:Insulin; D015676:Osteonectin; C577241:SPARC protein, human; D005947:Glucose