Key words: chromium, micronutrient, carbohydrate, lipid, metabolism, insulin, receptors, analysis, chromodulin, glucose, diabetes, glucose tolerance, factor,
Date: Oct 2006
Author: Morgan, G
Chromium has been shown to be an essential micronutrient involved in normal carbohydrate and lipid metabolism (Anderson 1985). Research has focused on its role in carbohydrate metabolism and, recently, the interactions of the biologically active form of chromium with insulin receptors has become an important area of research. The following relate to this area of research:
a) Chromium analysis
Problems of background contamination have bedevilled accurate analysis of the very low levels of chromium in the body. Veillon in 1989 reported that plasma and serum chromium was virtually undetectable with the then current instrumentation. In 1999 he reported that current instrumentation was now able to detect levels of chromium some 1000 times less than a decade or so before (Veillon 1999). This increase in sensitivity has in large measure been due to more sophisticated facilities for correcting background contamination. Earlier systems of atomic absorption spectroscopy using deuterium have been replaced with tungsten-halogen correctors with vastly improved sensitivity. The latest systems using a Zeeman-effect background correction are even more sensitive.
Sample collection, storage, preparation and analysis remain critical in working with chromium samples. Contamination is easily introduced: the use of specialised plastic containers, freezing to control water vaporization, the application of strict protocols and the implementation of the strictest in-house quality control procedures by specialised laboratories is essential if valid results are to be achieved.
b) Low molecular weight
chromium binding substance (LMWCr)
Research has identified the presence of a low molecular weight oligopeptide which binds chromium present in the blood in a transferring form enabling insulin receptors on cell surfaces to be activated (Yamamoto 1989, Vincent 1999). The oligopeptide contains only the four amino acids glycine, cysteine, glutamate and aspartate, has a molecular weight of around 1500 and is thought to bind four Cr3+ ions. Binding results in the inactive apo- form being changed into the active LMWCr or ‘chromodulin’ form. It is this form which is able to bind with insulin/insulin receptor sites to form complexes which initiate a series of kinase-mediated cascades associated with glucose metabolism (Davis 1996, Davis 1997). LMWCr not only fulfils a key role in glucose metabolism but the oligopeptide also binds to chromium in this form and is excreted in the bile and urine (Wada 1983, Manzo 1983). As such it may be implicated in the increased urinary excretion of chromium and the possible chromium- mediated renal pathology of diabetes mellitus (Morris 1992). Further research is needed in this area.
c) Glucose tolerance factor
The term glucose tolerance factor (GTF) was coined by Schwarz and Mertz (1957) to describe a substance which was able to reverse the biochemical changes associated with impaired glucose tolerance. Two forms have been described, one from acid-hydrolysed porcine kidney powder and the other from Brewer’s yeast. The latter has been extensively studied so that GTF usually refers exclusively to this form of bound chromium. Due to its increased biological activity it was thought that the chromium bound in GTF owed its insulin-binding activity to the presence of a bioactive macromolecule. Analysis of Brewer’s yeast GTF showed it to be a complex of chromium, nicotinic acid, glycine, glutamic acid and cysteine but, contrary to expectations its glucose lowering activity appears to be diminished rather than potentiated in the presence of insulin (Vincent 1994). Vincent also commented upon the relationship between GTF and LMWCr (Vincent 1994). It is now thought that GTF simply represents a more readily bioavailable source of chromium. It is of some interest as the picolinate form of chromium, now widely used as a supplement, was developed as a by-product of research into chromium-nicotinate complexes.
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