title: GLP-1 and glucagon secretion from a pancreatic neuroendocrine tumor causing diabetes and hyperinsulinemic hypoglycemia.
abstract: BACKGROUND
  Glucagon-like peptide-1 (GLP-1) is a gut peptide that promotes insulin release from pancreatic β-cells and stimulates β-cell hyperplasia. GLP-1 secretion causing hypoglycemia has been described once from an ovarian neuroendocrine tumor (NET) but has not been reported from a pancreatic NET (pNET).
  
  
  OBJECTIVE
  A 56-yr-old male with a previous diagnosis of diabetes presented with fasting hypoglycemia and was found to have a metastatic pNET secreting glucagon. Neither the primary tumor nor metastases stained for insulin, whereas the resected normal pancreas showed histological evidence of islet cell hyperplasia. We provide evidence that GLP-1 secretion from the tumor was the cause of hyperinsulinemic hypoglycemia.
  
  
  METHODS
  GLP-1 levels were determined in the patient, and immunohistochemistry for GLP-1 was performed on the tumor metastases. Ex vivo tissue culture and a bioassay constructed by transplantation of tumor into nude mice were performed to examine the tumor secretory products and their effects on islet cell function.
  
  
  RESULTS
  The patient had high levels of glucagon and GLP-1 with an exaggerated GLP-1 response to oral glucose. Immunohistochemistry and primary tissue culture demonstrated secretion of glucagon and GLP-1 from the tumor metastases, whereas insulin secretion was almost undetectable. Ex vivo coculture of the tumor with normal human islets resulted in inhibition of insulin release, and transplanted mice developed impaired glucose tolerance.
  
  
  CONCLUSIONS
  This is the first description of glucagon and GLP-1 secretion from a metastatic pNET causing sequential diabetes and hypoglycemia. Hypoglycemia was caused by insulin secretion from hyperplastic β-cells stimulated by tumor-derived GLP-1.
authors: King's College London School of Medicine, London SE1 1UL, United Kingdom.
authors: Rachel E
authors: RE
authors: Roberts
authors: Min
authors: M
authors: Zhao
authors: Ben C
authors: BC
authors: Whitelaw
authors: John
authors: J
authors: Ramage
authors: Salvador
authors: S
authors: Diaz-Cano
authors: Carel W
authors: CW
authors: le Roux
authors: Alberto
authors: A
authors: Quaglia
authors: Guo Cai
authors: GC
authors: Huang
authors: Simon J B
authors: SJ
authors: Aylwin
mesh_terms: D007516:Adenoma, Islet Cell / Q000150:complications / Q000378:metabolism / Q000601:surgery; D000818:Animals; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000209:etiology*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006498:Hepatectomy; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology*; D007003:Hypoglycemia / Q000209:etiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction; D013156:Splenectomy
chemical_list: D052216:Glucagon-Like Peptide 1; D005934:Glucagon