Radiolabeled glucagon-like peptide-1 analogues: a new pancreatic β-cell imaging agent.
ABSTRACT Glucagon-like peptide-1 (GLP-1) is a potent antihyperglycemic hormone. It can induce glucose-dependent insulin secretion. GLP-1 has a short half-life of less than 2 min in vivo due to degradation by the dipeptidyl peptidase-IV. GLP-l analogues, such as exendin-4 and exendin-3, have similar biological activity but a longer in-vivo half-life. Pancreatic β-cells and pancreatic islet cell tumors highly express GLP-1 receptors. Hence, radiolabeled GLP-1 analogues play a potential role in imaging and radiation therapy of pancreatic islet cell tumors as well as in the monitoring of pancreatic β-cell transplantation.
- New England Journal of Medicine 09/2008; 359(7):766-8. · 51.66 Impact Factor
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ABSTRACT: The recent identification in Heloderma horridum venom of exendin-3, a new member of the glucagon superfamily that acts as a pancreatic secretagogue, prompted a search for a similar peptide in Heloderma suspectum venom. An amino acid sequencing assay for peptides containing an amino-terminal histidine residue (His1) was used to isolate a 39-amino acid peptide, exendin-4, from H. suspectum venom. Exendin-4 differs from exendin-3 by two amino acid substitutions, Gly2-Glu3 in place of Ser2-Asp3, but is otherwise identical. The structural differences make exendin-4 distinct from exendin-3 in its bioactivity. In dispersed acini from guinea pig pancreas, natural and synthetic exendin-4 stimulate a monophasic increase in cAMP beginning at 100 pM that plateaus at 10 nM. The exendin-4-induced increase in cAMP is inhibited progressively by increasing concentrations of the exendin receptor antagonist, exendin-(9-39) amide. Unlike exendin-3, exendin-4 does not stimulate a second rise in acinar cAMP at concentrations greater than 100 nM, does not stimulate amylase release, and does not inhibit the binding of radiolabeled vasoactive intestinal peptide to acini. This indicates that in dispersed pancreatic acini, exendin-4 interacts only with the recently described exendin receptor.Journal of Biological Chemistry 05/1992; 267(11):7402-5. · 4.65 Impact Factor
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ABSTRACT: Endoscopic ultrasonography (EUS) and somatostatin receptor scintigraphy (SRS) can detect a high percentage of gastroenteropancreatic neuroendocrine tumours especially in the upper gastrointestinal tract. The ability of these procedures to localise primary tumour lesions and metastases of gastrinomas and insulinomas was evaluated in comparison with transabdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). In a prospective trial, patients with gastrinomas (n = 10) and insulinomas (n = 10) diagnosed by clinical signs and laboratory tests were assessed by EUS, SRS, US, CT and MRI. In 10 patients with gastrinoma and 10 patients with insulinoma, a total of 14 separate primary tumour lesions were histologically confirmed for each of the tumour entities. The mean diameter was 2.1 cm for gastrinomas and 1.5 cm for insulinomas. All insulinomas and nine gastrinoma lesions were located in the pancreas. Three gastrinomas were found in the duodenal wall, one in a periduodenal lymph node, and one in the liver, For gastrinomas, sensitivities were 79% with EUS, 86% with SRS and 29% with CT, US, and MRI. For insulinomas, sensitivities were 93% with EUS, 14% with SRS, 21% with CT and 7% with US and MRI. EUS is of high value for localising primary lesions of both tumour entities. SRS is a very sensitive procedure for diagnosing of gastrinomas but not insulinomas. CT, US and MRI are primarily useful for visualising metastases.Gut 11/1996; 39(4):562-8. · 10.73 Impact Factor