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Internalization of glucagon-like peptide-1(7–36)amide in rat insulinoma cells

  • Original Papers
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Research in Experimental Medicine

Summary

Glucagon-like peptide-1(7–36)amide [GLP-1(7–36)amide] is supposed to be an important physiologic incretin. Recently, high affinity receptors for GLP-1(7–36)amide have been demonstrated on rat insulinomaderived RINm5F cells. The present study examined the internalization and degradation of the GLP-1-receptor complex. Internalization of the peptide was time- and temperature-dependent. At 37°C binding and internalization was rapid. At 60 min 35% of125I-labeled GLP-1(7–36)amide was internalized. Incubation in the presence of increasing concentrations of nonlabeled GLP-1(7–36)amide resulted in a decrease of internalization of125I-labeled peptide indicating that this process is saturable. Incubation in the presence of 0.2 mM chloroquine, an inhibitor of intracellular hormone degradation, resulted in intracellular accumulation of125I-GLP-1(7–36)amide. HPLC-supported analysis of cell content after internalization of125I-GLP-1(7–36)amide during a 60-min incubation period at 37°C revealed an elution profile showing two maxima of radioactivity: one represented intact labeled GLP-1(7–36)amide, the other an intracellular degradation product of the peptide. Chloroquine caused a 5-fold increase of the peak representing intact125I-GLP-1(7–36)amide thus demonstrating inhibition of degradation of labelled peptide. Furthermore, a 4-fold increase of the other peak occurred possibly mirroring a delay of release of degradation products by chloroquine. It was excluded that chloroquine is able to interfere with GLP-1(7–36)amidebinding to its receptor.

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Authors and Affiliations

  1. Dept. of Internal Medicine, Division of Gastroenterology and Metabolism, Philipps University of Marburg, Baldinger Straße, D-3550, Marburg, Federal Republic of Germany

    R. Göke, G. Richter, B. Göke, M. Trautmann & R. Arnold

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  1. R. Göke
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  2. G. Richter
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  3. B. Göke
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  4. M. Trautmann
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  5. R. Arnold
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Göke, R., Richter, G., Göke, B. et al. Internalization of glucagon-like peptide-1(7–36)amide in rat insulinoma cells. Res. Exp. Med. 189, 257–264 (1989). https://doi.org/10.1007/BF01852257

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  • DOI: https://doi.org/10.1007/BF01852257

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