In vivo characterization of insulin uptake by dog renal cortical epithelium

Journal Article · Thu Sep 01 00:00:00 EDT 1988 · Am. J. Physiol.; (United States)

OSTI ID:6756017

Whiteside, C I; Lumsden, C J; Silverman, M

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.

• Research Organization: Univ. of Toronto, Ontario (Canada)
• OSTI ID: 6756017
• Journal Information: Am. J. Physiol.; (United States), Vol. 255
• Country of Publication: United States
• Language: English

Related Subjects

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