Background-The mechanism of iron absorption by the intestine and its transfer to the main iron storage site, the liver, is poorly understood. Recently an iron carrier was cloned and named DMT1 (divalent metal transporter 1). Aims-To determine the level of DMT1 gene expression and protein distribution in duodenum and liver. Methods-A DMT1 cRNA and antibody were produced and used in in situ hybridisation and immunohistochemistry, respectively, in rats in which the iron stores were altered by feeding diets with normal, low, and high iron content. Results-Duodenal DMT1 mRNA was low in crypts and increased at the crypt-villus junction in iron deficient and control rats; it fell in the iron loaded state. Staining for DMT1 protein was not detected in crypts. In villus enterocytes, protein staining was localised to the microvillus membrane in iron deficiency, in the cytoplasm and to a lesser extent in the membrane in controls, and entirely in the cytoplasm of iron loaded animals. Liver DMT1 mRNA was distributed evenly across hepatocytes. DMT1 protein staining was observed on hepatocyte plasma membranes, with highest values in the iron loaded state, lower values in control animals, and none after iron depletion. Conclusions-Results are consistent with a role for DMT1 in the transmembrane transport of non-transferrin bound iron from the intestinal lumen and from the portal blood. (Gut 2000;46:270-276)

Gastrin is transiently expressed in fetal islets during a critical period of their development from protodifferentiated islet precursors in fetal pancreatic ducts. To examine the possible role of gastrin as an islet cell growth factor, postnatal islet growth was studied in transgenic mice which overexpress gastrin and TGFa in their pancreas. Overexpression of a TGFa transgene causes metaplastic ductules containing numerous insulin expressing cells that resemble protodifferentiated precursors of the fetal pancreas. However, islet mass of the TGFa transgenic mice was not increased. Pancreatic overexpression of gastrin from a chimeric insulin/gastrin transgene transcribed from the insulin promoter markedly decreased the TGFa-stimulated increase in pancreatic duct mass. Furthermore, pancreatic coexpression of both gastrin and TGFa significantly increased islet mass in mice expressing both transgenes. These findings indicate that TGFa and gastrin can act synergistically to stimulate islet growth, although neither peptide alone is sufficient. Islet growth may possibly be stimulated through gastrin promoting the differentiation of insulin-positive cells in the TGFa-induced metaplastic ducts. This transgenic study suggests that islet neogenesis can be reactivated in the ductular epithelium of the adult pancreas by local expression of two growth factors, gastrin and TGFa. (J. Clin. Invest. 1993. 92:1349-1356

THE IMPORTANCE OF DIETARY IRON AND HEMEIron is a vitally important element in biological terms (for review see [1] ). Iron is a transition metal with the ability to readily accept and donate electrons, allowing it to function as an oxidant or reductant in a large number of biochemical reactions. In mammals, iron is notably required for oxygen transport as a component of hemoglobin, DNA synthesis as a component of ribonucleotide reductase, and as an electron acceptor/ donor in the cytochromes that are essential for energy transduction. Currently, iron deficiency is the most common diet related health problem in the world [2] , and the effects on human health are wide ranging. Iron deficiency manifests as anaemia in up to 2 billion people, impairs physical and mental development in children, and can exacerbate many other health problems.Heme is a biologically important iron containing compound and a key source of dietary iron. Historically, it was doubted that heme iron could be absorbed by the enterocyte and it was not until 1955 that the absorption of heme-derived iron was demonstrated for the first time [3] . Currently, the importance of heme iron in the diet cannot be underestimated. Studies estimate that in Western societies, iron derived from heme sources such as myoglobin and hemoglobin make up twothirds of the average person's total iron stores despite only constituting one-third of the iron that is actually ingested [4][5][6] . This likely explains why vegetarians are more prone to iron deficiency than those who regularly consume red meat [7] . T h e r e l a t ive i m p o r t a n c e o f d i e t a r y h e m e i s attributable to its high bioavailability compared with AbstractIron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heme absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heme transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a nonheme iron transport protein may be required for heme iron absorption and discuss the experiences of our laboratory in examining this hypothesis.

No abstract

No abstract