Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass.
OBJECTIVE
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
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.
Reubi
J C
JC
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, PO Box 62, Murtenstrasse 31, CH-3010 Berne, Switzerland. reubi@pathology.unibe.ch
Perren
A
A
Rehmann
R
R
Waser
B
B
Christ
E
E
Callery
M
M
Goldfine
A B
AB
Patti
M E
ME
D000328:Adult; D000368:Aged; D001345:Autoradiography; D005260:Female; D015390:Gastric Bypass / Q000009:adverse effects / Q000534:rehabilitation; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007003:Hypoglycemia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D018027:Receptors, Glucagon / Q000378:metabolism*; D012720:Severity of Illness Index; D015854:Up-Regulation
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon