Summary
We have searched for the contribution of the kidney to the catabolism of glucagon-like
peptide-1 (7-36)amide or tGLP-1 by analyzing the disappearance of the [125I]tGLP-1 both in vivo, from the plasma of bilaterally nephrectomized (BNX), ureteral-ligated
(BUL) and normal rats and in vitro from the perfusate of an isolated rat kidney system.
Also, we have measured the degradation of the peptide by the isolated renal tubules.
Results from in vivo studies demonstrated that the disappearance half-time (t1/2)
of [125I]tGLP-1 was significantly lower in the control than in BUL or BNX rats with the metabolic
clearance rate (MCR) being higher in the control than in BUL and BNX group; no difference
was found for both parameters between BUL and BNX rats. The urinary excretion of the
peptide was negligible. The data from the isolated kidney experiments showed a disappearance
of the peptide, which was not due to its spontaneous degradation nor to enzymes released
from the kidney to the perfusate. Degradation of the peptide also occurred in the
presence of isolated tubules. It was dependent upon the concentration of tubules.
This could possibly be due to the action of the brush border-associated peptidases.
In conclusion, our results demonstrate that, in the rat, the kidney removes the exogenous
tGLP-1 from the peripheral circulation, by a mechanism that involves glomerular filtration
and tubular catabolism.
Key words
GLP-1(7-36)Amide - Renal Catabolism - Metabolic Clearance
