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

Reubi, J. ; Perren, A. ; Rehmann, R. ; Waser, B. ; Christ, E. ; Callery, M. ; Goldfine, A. ; Patti, M.

In: Diabetologia, 2010, vol. 53, no. 12, p. 2641-2645

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    Titel
    • Glucagon-like peptide-1 (GLP-1) receptors are not overexpressed in pancreatic islets from patients with severe hyperinsulinaemic hypoglycaemia following gastric bypass
    Autor
    • Reubi, J.. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, CH-3010, Berne, Switzerland
    • Perren, A.. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, CH-3010, Berne, Switzerland
    • Rehmann, R.. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, CH-3010, Berne, Switzerland
    • Waser, B.. Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, CH-3010, Berne, Switzerland
    • Christ, E.. Divisions of Endocrinology, Diabetology, and Clinical Nutrition, Inselspital, University Hospital of Berne, Berne, Switzerland
    • Callery, M.. Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
    • Goldfine, A.. Research Division, Joslin Diabetes Center, Boston, MA, USA
    • Patti, M.. Research Division, Joslin Diabetes Center, Boston, MA, USA
    Dokumententyp
    • Postprint
    OAI-PMH-ID
    • oai:doc.rero.ch:312163
    Summary
    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 ± 183dpm/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 ± 104dpm/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 ± 1,073dpm/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