title: Are biochemical markers of neuroendocrine tumors coreleased with insulin following local calcium stimulation in patients with insulinomas?
abstract: OBJECTIVE
  The objective was to test whether chromogranin A (CgA), neuron-specific enolase (NSE), and pancreatic polypeptide (PP) are released from the pancreas during the selective arterial calcium stimulation and hepatic venous sampling test (ASVS) in patients with insulinomas.
  
  
  METHODS
  We determined CgA, NSE, PP, insulin, C-peptide, and proinsulin in blood samples obtained during the ASVS test in 19 patients with insulinomas. Levels following calcium injection into the arteries supplying the tumor were compared with levels following calcium stimulation of arteries supplying healthy pancreatic tissue.
  
  
  RESULTS
  After calcium injection into the artery supplying the insulinoma, a significant 8-fold increase in insulin (range, 2.3-117; P < 0.001), a 3.8-fold increase in C-peptide (1.7-32.4; P < 0.001), and a 1.9-fold increase in proinsulin (0.7-5.3, P < 0.001) were detectable whereas NSE and CgA did not increase. No significant increases in insulin, C-peptide, proinsulin, CgA, and NSE concentrations were found after calcium injection into control arteries. Pancreatic polypeptide increased 1.5-fold (0.8-4.5; P = 0.017) after calcium injection into the tumor artery and 2.4-fold (0.8-7.9; P = 0.016) after injection into the control artery.
  
  
  CONCLUSIONS
  Insulin, C-peptide, and proinsulin are released by insulinoma cells in response to arterial calcium stimulation, whereas CgA and NSE are not released. Also from our study it seems that PP may be released by healthy islet cells after calcium stimulation.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetes, Kantonsspital Frauenfeld, Frauenfeld, Switzerland. peter.wiesli@stgag.ch
authors.forename: Peter
authors.initials: P
authors.lastname: Wiesli
authors.forename: Heiko
authors.initials: H
authors.lastname: Uthoff
authors.forename: Aurel
authors.initials: A
authors.lastname: Perren
authors.forename: Thomas
authors.initials: T
authors.lastname: Pfammatter
authors.forename: Cornelia
authors.initials: C
authors.lastname: Zwimpfer
authors.forename: Heidi
authors.initials: H
authors.lastname: Seiler
authors.forename: René
authors.initials: R
authors.lastname: Kindhauser
authors.forename: Giatgen A
authors.initials: GA
authors.lastname: Spinas
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D002125:Calcium Gluconate / Q000008:administration & dosage; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D007328:Insulin / Q000097:blood*; D007340:Insulinoma / Q000097:blood / Q000098:blood supply / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000098:blood supply / Q000175:diagnosis*; D010191:Pancreatic Polypeptide / Q000097:blood*; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood*; D013557:Switzerland
chemical_list: D014408:Biomarkers, Tumor; D002096:C-Peptide; D053379:Chromogranin A; D007328:Insulin; C043710:PPY protein, human; D011498:Protein Precursors; D010191:Pancreatic Polypeptide; D010751:Phosphopyruvate Hydratase; D002125:Calcium Gluconate