title: Characterization of insulin uptake into subcellular fractions of perfused rat liver using two different iodinated tracers.
abstract: The binding and uptake of insulin in perfused rat liver has been investigated with specifically labelled 125I-A14-tyrosyl insulin as a tracer and compared with a commercially available iodo-insulin preparation. The commercial preparation did not show saturation uptake kinetics and the clearance from the perfusate remained low and constant throughout a wide concentration range. A14 labelled insulin showed saturation kinetics and high clearance at low carrier concentration, falling rapidly with increasing carrier concentration and reaching a steady state value of 1 ml/min. These results emphasize the importance of using specifically labelled insulin in physiological and biochemical studies of hepatic insulin metabolism. Perfusion with A14 tyrosine-labelled insulin at 4 degrees C showed apparent saturation with binding to the plasma membrane fraction. Perfusion at 37 degrees C also showed apparent saturation with uptake predominantly to the ligandosome fraction. These results implicate the plasma membrane-ligandosome pathway in the hepatic uptake of insulin at both physiological and pharmacological concentrations of the hormone.
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D013696:Temperature
chemical_list: D007328:Insulin; D007457:Iodine Radioisotopes; C008147:insulin, iodo-; C029491:insulin, 3-iodo-Tyr(A14)-