(Journal Article): Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells.
 
Goke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, Goke B (Department of Internal Medicine, Philipps University of Marburg, Germany.)
 
IN: J Biol Chem 1993; 268(26):19650-19655
Impact Factor(s) of J Biol Chem: 6.355 (2004), 6.482 (2003), 7.258 (2001)

Fulltext:    PDF

ABSTRACT: Exendin-4 purified from Heloderma suspectum venom shows structural relationship to the important incretin hormone glucagon-like peptide 1-(7-36)-amide (GLP-1). We demonstrate that exendin-4 and truncated exendin-(9-39)-amide specifically interact with the GLP-1 receptor on insulinoma-derived cells and on lung membranes. Exendin-4 displaced 125I-GLP-1, and unlabeled GLP-1 displaced 125I-exendin-4 from the binding site at rat insulinoma-derived RINm5F cells. Exendin-4 had, like GLP-1, a pronounced effect on intracellular cAMP generation, which was reduced by exendin-(9-39)-amide. When combined, GLP-1 and exendin-4 showed additive action on cAMP. They each competed with the radio-labeled version of the other peptide in cross-linking experiments. The apparent molecular mass of the respective ligand-binding protein complex was 63,000 Da. Exendin-(9-39)-amide abolished the cross-linking of both peptides. Exendin-4, like GLP-1, stimulated dose dependently the glucose-induced insulin secretion in isolated rat islets, and, in mouse insulinoma beta TC-1 cells, both peptides stimulated the proinsulin gene expression at the level of transcription. Exendin-(9-39)-amide reduced these effects. In conclusion, exendin-4 is an agonist and exendin-(9-39)-amide is a specific GLP-1 receptor antagonist.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Gallwitz B. New Therapeutic Strategies for the Treatment of Type 2 Diabetes Mellitus Based on Incretins. Rev Diabetic Stud 2005. 2: 61-69.
  » Diabetes OD » Disease Management » T2DM » Metabolic Control » Anti-Hyperglycemic and Anti-Ap... » Incretin Hormones » GLP-1 » Effectivity of GLP-1 in Therap... » Journal Article