Chromium is an essential trace mineral in mammals that is required for the metabolism of lipids and carbohydrates due to its role in the function of the insulin receptor. Chromium is needed by mammals in its trivalent form [Cr(III)], but details of kinetics in humans have been slow to accumulate due to its low tissue concentration and its inertness in substitution (exchange) reactions. Little is known about deficiencies of chromium in humans, but animals studies have elucidated the mechanisms of chromium deficiency induced diabetes. Chromium was established as essential in rats in the 1950s following studies feeding rats diets devoid of chromium, whereby symptoms of elevated blood glucose were reversed upon administration of chromium. The essentiality of chromium in humans was established through similar reasoning in patients receiving total parenteral nutrition who developed diabetic symptoms which were reversed on the administration of chromium.
Studies investigating the role of chromium in humans have been inconclusive, mainly because of the difficulty in determining the chromium status of an individual prior to supplementation. The difficulty of analysing chromium in mammalian tissue is illustrated by the fact that prior to 1980, there was no analytical technique sensitive enough to distinguish tissue chromium from sample contamination during processing. The absorption of chromium is not fully understood, but chromium is thought to be absorbed in the jejunum by either diffusion or carrier mediated mechanisms. Absorption of chromium is poor, with absorption varying from around 0.5 to 2% with intakes of 40 and 10µg, respectively. Brewer’s years is known to reverse the symptoms of diabetes in rats because of the presence of chromium. Isolation of chromium in brewer’s yeast has shown that the chromium is present as an organic complex bound to glutathione and nicotinic acid.
The function of chromium in mammals is dependent chromodulin, a low molecular weight binding protein (1500 Da) consisting of glycine, glutamate, aspartate and cysteine residues. The complex also contain nicotinic acid as is sometimes referred to as the glucose tolerance factor (GTF), the same molecule as found in brewer’s yeast. Chromodulin is able to potentiate the effects of insulin in insulin dependent cells. One current model suggests that when insulin binds to the insulin receptor, the receptor is converted from the inactive to the active form. This stimulates the transfer of chromium from the blood into the cells via the transfer protein transferin. The chromium then binds to apochromodulin, which then subsequently binds to the insulin receptor. This potentiates the activity of insulin by activating the tyrosine kinase signal transduction that causes phosphorylation of the receptor, a step that is required in order to potentiate the activity of insulin inside the cell.
As the insulin concentration of plasma falls, the chromodulin is released back into the cell, and subsequently excreted to the plasma and urine. Because the activity of chromodulin is dependent on the chromium content of the molecule, low levels of chromium in plasma will limit the signal caused by insulin binding to its receptor. This will therefore decrease glucose uptake from the plasma to the cell and cause the hyperglycaemia and diabetic symptoms seen in humans and animals in the early observations of chromium deficiency. Whether diabetes in humans is the result in part or whole by a deficiency of chromium is not known, but evidence suggests that chromium deficiency could play a participatory role. Reversal of diabetic symptoms by the administration of a chromium supplement or a chromium rich diet would confirm a causative role for chromium deficiency in the development of diabetes.
RdB
