Horm Metab Res 1998; 30(8): 514-517
DOI: 10.1055/s-2007-978923
Originals Experimental

© Georg Thieme Verlag Stuttgart · New York

Nephrectomy Decreases Amylin and Pramlintide Clearance in Rats

W. Vine, P. Smith, R. LaChappell, E. Blase, R. Lumpkin, A. Young
  • Amylin Pharmaceuticals Inc., San Diego, CA, USA
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Publikationsverlauf

1997

1998

Publikationsdatum:
20. April 2007 (online)

Amylin is a 37 amino acid hormone, co-secreted with insulin from the pancreatic β-cell in response to nutrient stimuli. Because the human amylin analog, pramlintide, is being tested in patients with diabetes mellitus, a known risk factor for nephropathy, we examined the role of the kidney on amylin and pramlintide metabolism and action in functionally nephrectomized rats. Nephrectomy markedly altered amylin metabolism: it increased incremental area under the plasma amylin concentration curve 3.6-fold (P < 0.001) and increased the elimination half-life from 17 ± 1 to 26 ± 2 minutes (P < 0.01) after subcutaneous injection of 100 µg amylin. Nephrectomy decreased plasma amylin clearance from 20.3 ± 1.1 to 7.9 ± 0.4 mL/min (P < 0.0001). Thus, at these doses in the rat, the kidney is important for metabolizing amylin and pramlintide.