Nephrectomy decreases amylin and pramlintide clearance in rats.
Amylin is a 37 amino acid hormone, co-secreted with insulin from the pancreatic beta-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 microg 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.
Amylin Pharmaceuticals Inc., San Diego, CA 92121, USA.
W
W
Vine
P
P
Smith
R
R
LaChappell
E
E
Blase
R
R
Lumpkin
A
A
Young
D000682:Amyloid / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; D019344:Lactic Acid; C105254:pramlintide; D002118:Calcium