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Title: In vivo characterization of insulin uptake by dog renal cortical epithelium

Abstract

In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: (3H)dextran greater than 70 kDa (plasma reference), (14C)inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below (14C)inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching (14C)inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. Inmore » vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM.« less

Authors:
; ;
Publication Date:
Research Org.:
Univ. of Toronto, Ontario (Canada)
OSTI Identifier:
6756017
Resource Type:
Journal Article
Journal Name:
Am. J. Physiol.; (United States)
Additional Journal Information:
Journal Volume: 255
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; INSULIN; MEMBRANE TRANSPORT; MATHEMATICAL MODELS; CARBON 14 COMPOUNDS; CELL MEMBRANES; DOGS; EPITHELIUM; IN VIVO; INULIN; IODINE 125; TRACER TECHNIQUES; TRITIUM COMPOUNDS; TUBULES; ANIMAL TISSUES; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; CARBOHYDRATES; CELL CONSTITUENTS; DAYS LIVING RADIOISOTOPES; ELECTRON CAPTURE RADIOISOTOPES; HORMONES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; KIDNEYS; LABELLED COMPOUNDS; MAMMALS; MEMBRANES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PEPTIDE HORMONES; POLYSACCHARIDES; RADIOISOTOPES; SACCHARIDES; TISSUES; VERTEBRATES; 551001* - Physiological Systems- Tracer Techniques

Citation Formats

Whiteside, C I, Lumsden, C J, and Silverman, M. In vivo characterization of insulin uptake by dog renal cortical epithelium. United States: N. p., 1988. Web.
Whiteside, C I, Lumsden, C J, & Silverman, M. In vivo characterization of insulin uptake by dog renal cortical epithelium. United States.
Whiteside, C I, Lumsden, C J, and Silverman, M. 1988. "In vivo characterization of insulin uptake by dog renal cortical epithelium". United States.
@article{osti_6756017,
title = {In vivo characterization of insulin uptake by dog renal cortical epithelium},
author = {Whiteside, C I and Lumsden, C J and Silverman, M},
abstractNote = {In vivo 125I-labeled insulin uptake by dog renal tubular epithelium was studied using the single-pass multiple indicator dilution (MID) method and analyzed by a computer-assisted model of transcapillary exchange and substrate-cell interaction. Anesthetized dogs received an intrarenal arterial bolus of multiple tracers: (3H)dextran greater than 70 kDa (plasma reference), (14C)inulin (extracellular reference), and 125I-insulin. Rapid serial sampling of the renal venous and urine outflows was performed. The renal venous outflow curves of 125I-insulin fell below (14C)inulin implying postglomerular extraction and antiluminal membrane (ALM) uptake. The fractional urine recovery of 125I-insulin was less than 0.03, indicating luminal tubular uptake of filtered hormone. After intravenous infusion of unlabeled insulin, repeat MID runs with tracer revealed saturable ALM uptake as evidenced by the 125I-insulin renal venous outflow curves approaching (14C)inulin. Luminal tubular uptake was unchanged and therefore unsaturable. The 125I-insulin renal venous data were studied using three mathematical models, incorporating postglomerular reversible binding, irreversible binding or transport. The best fit was obtained using the transport model. The modeling analysis is consistent with either uptake into a virtual epithelial membrane space (i.e., insulin never enters the cell but binds to or is distributed along the ALM) or insulin actually enters the intracellular compartment. In vivo uptake of 125I-insulin ALM is characterized by a Km of 15.44 nM.},
doi = {},
url = {https://www.osti.gov/biblio/6756017}, journal = {Am. J. Physiol.; (United States)},
number = ,
volume = 255,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1988},
month = {Thu Sep 01 00:00:00 EDT 1988}
}