Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass

Diabetologia. 2010 Dec;53(12):2641-5. doi: 10.1007/s00125-010-1901-y. Epub 2010 Sep 14.

Abstract

Aims/hypothesis: Glucagon-like peptide-1 (GLP-1) receptors are highly overexpressed in benign insulinomas, permitting in vivo tumour visualisation with GLP-1 receptor scanning. The present study sought to evaluate the GLP-1 receptor status in vitro in other pancreatic disorders leading to hyperinsulinaemic hypoglycaemia, specifically after gastric bypass surgery.

Methods: Fresh frozen pancreatic tissue samples (n=7) from six gastric bypass surgery patients suffering from hyperinsulinaemic hypoglycaemia were evaluated for GLP-1 receptor content using in vitro receptor autoradiography, and compared with normal pancreas and with pancreatic insulinoma tissues.

Results: GLP-1 receptor analysis of the pancreatic tissues, which histopathologically were compatible with nesidioblastosis and originated from post-bypass hypoglycaemic patients, revealed a mean density value of GLP-1 receptors in the islets of 1,483 ± 183 dpm/mg tissue. Pharmacological characterisation indicated the presence of specific GLP-1 receptors. The density of islet GLP-1 receptor in post-gastric bypass patients did not differ from that of normal pancreas (1,563 ± 104 dpm/mg tissue, n = 10). Receptor density in pancreatic acini was low in post-bypass and control conditions. In contrast, benign insulinomas showed a high density of GLP-1 receptors, with a mean value of 8,302 ± 1,073 dpm/mg tissue (n = 6).

Conclusions/interpretation: In contrast to insulinoma, hyperinsulinaemic hypoglycaemia after gastric bypass surgery is not accompanied by overexpression of GLP-1 receptor in individual islets. Thus, patients with post-gastric bypass hyperinsulinaemic hypoglycaemia are not candidates for GLP-1 receptor imaging in vivo using radiolabelled exendin. These GLP-1 receptor data support the notion that the islet pathobiology of post-gastric bypass hypoglycaemia is distinctly different from that of benign insulinomas.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoradiography
  • Female
  • Gastric Bypass* / adverse effects
  • Gastric Bypass* / rehabilitation
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hyperinsulinism / complications
  • Hyperinsulinism / metabolism*
  • Hyperinsulinism / pathology
  • Hypoglycemia / etiology
  • Hypoglycemia / metabolism*
  • Hypoglycemia / pathology
  • Insulinoma / metabolism
  • Insulinoma / pathology
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Middle Aged
  • Obesity, Morbid / metabolism
  • Obesity, Morbid / pathology
  • Obesity, Morbid / surgery*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Receptors, Glucagon / metabolism*
  • Severity of Illness Index
  • Up-Regulation

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon