ABSTRACT
Two aspects of the mechanisms by which iron is absorbed by the intestine were studied in the Caco2 cell model, using 59Fe(II)-ascorbate. Data showing the importance of vesicular processes and cycling of apotransferrin (apoTf) to uptake and overall transport of Caco2 cell monolayers (or basolateral 59Fe release) were obtained by comparing effects of: a) adding apoTf to the basal chamber; b) adding vesicular transport inhibitors; or c) cooling to 4°C. These showed that apoTf may be involved in as much as half of Fe transfer across the basolateral membrane, and that vesicular processes may also play a role in non-apoTf-dependent Fe transport. Studies were initiated to examine potential interactions of other metal ions with Fe(II) via DMT1. Kinetic data showed a single, saturable process for uptake of Fe(II) that was pH dependent and had a Km of 7 ìM. An excess of Mn(II) and Cu(I) over Fe(II) of 200: 1 (ìM: ìM) in 1 mM ascorbate markedly inhibited Fe uptake. The kinetics were not competitive. Km increased and Vmax decreased. We conclude that vesicular transport, involving endo- and exocytosis at both ends of the enterocyte, is a fundamental aspect of intestinal iron absorption and that DMT1 may function as a transporter not just for divalent but also for monovalent metal ions.
Subject(s)
Animals , Humans , Rats , Apoproteins/pharmacokinetics , Ascorbic Acid/pharmacokinetics , Cation Transport Proteins/pharmacokinetics , Ferrous Compounds/pharmacokinetics , Intestinal Absorption/physiology , Transferrin/pharmacokinetics , Vesicular Transport Proteins/metabolism , Biological Transport, Active , /metabolism , Drug Interactions , Endocytosis , Vesicular Transport Proteins/antagonists & inhibitorsABSTRACT
The advances in the study of the role of growth hormone (GH) in the field of diabetes, confining clinically its glucoregulatory and diabetogenic effects, plus relevant findings in basic research, open new perspectives. The influence of GH on Type-2 diabetes is based on the classic experiments of Houssay's school, the diabetogenic action of GH and its transferrin mediator. Since GH is under hypothalamic command, the permanent GH hypersecretion is the pathophysiological evidence for hypothalamic dysfunction. Thus, type-2 diabetes is postulated as a reversible type of clinical idiohypohyseal diabetes. Different degrees of hypophyseal diabetes can be observed, with the interplay between insulin-growth factor-l and transferrin in some cases of acromegaly. In cases of selective predominance of GH and the consequent chronic elevation of transferrin levels, idiohypophyseal diabetes would develop. Therefore, this type of diabetes should be treated with hypothalamic GH inhibitors. In this line of thinking, the use of somatostatin analogs looks promising
Subject(s)
Humans , Animals , Diabetes Mellitus, Type 2/physiopathology , Transferrin/pharmacokinetics , Somatostatin , Human Growth Hormone , Diabetic Nephropathies/physiopathologyABSTRACT
Se determina hierro sérico, capacidad total de fijación de hierro, capacidad latente de fijación de hierro y por ciento de saturación de la transferrina en 30 vegetarianos y en 18 no vegetarianos hombres y mujeres adultos. No se han encontrado diferencias estadísticamente significativas para los exámenes realizadas en vegetarianos. Sin embargo el reducido número de muestras realizadas no permite dar una conclusión definitiva.