PETER R. FLATT* and PER-OLOF BERGGRENt. *Division of Nutrition and ... nutritional role (Doisy et al., 1976; Underwood, 1977; Shapcott. & Hubert, 1979).
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Distribution of chromium in the tissues of normal and genetically diabetic mice example, administration of G T F to genetically diabetic mice with coexistent hyperglycaemia and hyperinsulinaemia resulted in a partial amelioration of the diabetes (Tuman & Doisy, 1977). Satisfactory methods for the analysis of chromium in biological specimens have become available so recently that reliable data on the tissue distribution are both sparse and Although chromium is included in the group of 26 trace sporadic. In the present study electrothermal atomic-absorption elements considered to be essential for mammalian life, much spectrometry has been used to determine chromium in various remains to be established concerning its biochemistry and tissues and fluids of normal and genetically obese-hypernutritional role (Doisy et al., 1976; Underwood, 1977; Shapcott glycaemic (oblob) mice. & Hubert, 1979). The element has been linked to the Mice derived from the Aston colony (Flatt & Bailey. 1981) maintenance of efficient glucose homoeostasis. Thus. as an were used at 17-26 weeks of age. They were maintained on a integral component of GTFS, tirvalent chromium is generally standard pellet diet (Spratts laboratory diet no. I ; Lillico Ltd., believed to act as a cofactor for insulin (Shapcott & Hubert, Reigate, Surrey, U.K.) and tap water ad libitum. Blood was 1979). The exact structure of G T F is also undetermined, but it collected from fed mice by cardiac puncture. The separated apparently comprises two nicotinic acid molecules per Cr3+ plasma and small pieces (approx. IOOpg) of the tissues listed in atom as well as cysteine, glycine and possibly glutamic acid Table 1 were freeze-dried overnight before chromium analysis. residues. A possible analogy therefore exists between G T F and In one series of experiments, the mice were injected intravitamin B,, (cyanocobalamin), which contains the trace element peritoneally with 2 mg of tervalent chromium chloride (CrCI,, cobalt. 6H,O)/kg 96 h previously. Total chromium was determined in Many studies have shown that dietary restriction of reconstituted fluids or dried tissues essentially as described by chromium leads to an impairment of glucose tolerance which Liden & Lundberg (1979) by using a CRA-90 graphite furnace can be readily reversed by supplementation with Cr3+ salts or mounted on a single-beam Varian-Techtron AA-6 atomicpreformed G T F derived from brewer's yeast (Doisy et al., 1976: absorption spectrometer. A three-step temperature programme Underwood, 1977). However, unlike some trace elements, was used, involving drying for 40s at 100°C, ashing for 45 s at evidence suggests that chromium deficiency is quite prevalent in 70O0C, and atomization for 3 s at 2400OC. The graphite tube some populations, owing to inadequate intake, poor availability was flushed with argon at a flow rate of 5litres/min and the or impaired utilization (Shapcott & Hubert, 1979). Indeed, the spectrometer was operated at a wavelength of 357.9nm with a last abnormality has been partly implicated in the expression of spectral band-pass of 0.2 nm. Under these operating conditions, glucose interolerance by humans and animals with spontaneous a linear relationship existed between the peak absorbance and diabetes mellitus (Doisy et al., 1976; Underwood, 1977). For increasing amounts of chromium up to 8pmol. The precision and reproducibility of the method were high, and no interference 1: Abbreviation: GTF, glucose-tolerancefactor. was found with any of the more common transition metals. Consistent with its classification as an essential trace element, small amounts of chromium were distributed widely in the Table 1. Distribution of chromium in tissues and body fluids tissues and body fluids (Table I). No significant differences were of lean and genetically obese-hyperglycaemic (oblob) mice noted between the two genotypes either before or after Cr3+ Amounts of chromium are given as m e a n s k ~ . ~ for . ~ . the administration. However, whereas the chromium content of numbers of mice given in parentheses. The increments 96 h after urine and several tissues were increased in lean mice after Cr3+ intraperitoneal injection of 2mg of CrCI,, 6H,O/kg are given injection, no changes were observed in the obese mutant. The for those tissues which contained significantly more chromium diabetic state is therefore associated with the rapid excretion of (at least P < 0.05): *P < 0.05,t P < 0.02, SP < 0.01 compared chromium and an inability to utilize Cr'+, rather than an < 0.05, bP< 0.02, cP < 0.01 actual deficiency of the element. It is also noteworthy that the with endocrine pancreas: compared with exocrine pancreas: all evaluated by Student's t secretory glands of lean mice (pituitary, testes and both test (NS, no significant change). There were no significant divisions of the pancreas) differed from liver, kidney, muscle differences between lean and obese-hyperglycaemic mice. and spleen in the retention of exogenous chromium. However, compared with other tissues of untreated mice, the exocrine Chromium in body tissues (pmol/kg) pancreas and endocrine pancreatic islets of both genotypes or body fluids (nmol/l) A were particularly rich in chromium. This suggests a hitherto I \ Lean mice Obese mice unrecognized link between the trace element and the function of & & the pancreatic glands. Tissue or fluid Amount of Cr Increment Amount of Cr Increment 1.5fO.5 (13)'kC 5 . 1 ~ 2.2k 1.2 (5)tb NS Liver We are pleased to acknowledge the British Council and the Kidney 1.3 f0.5 (7). 7.1 x 5.4k2.2 (6)tb NS Federation of European Biochemical Societies for financial assistance. Skeletal muscle 2.5 f 0.6 (9)*" 7.6 x 6.8 f 4.0 (4)'kh N S Cardiacmuscle 1.1 f0.3 (5) 7 . 6 ~ 9.4k4.5 (6)th NS Doisy, R. J., Streeten, D. H. P., Freiberg, J. M. & Schneider, A. J. Exocrine 34.7f 13.5 (9) NS 64.7f 14.5 (1 I ) NS (1976) in Trace Elements in Human Nutrition and Disease (Pfasad, pancreas A. S., ed.), vol. 2, pp. 78-104, Academic Press. London Endocrine 58. I f 33.6 (5) NS 55.4 -t 14.5 (7) NS Flatt, P. R.& Bailey, C. J. (1981) Diabetologia 20, 573-577 pancreas Liden, S. & Lundberg. E. ( 19791J. h e s t . Dermatof. 7 2 42-45 NS 1.6f0.5 (5) 7 . 8 ~ 4.7f2.6(6)Sb Spleen Shapcott, D. & Hubert, J. (eds.) (1979) Chromium in Nutrition and 7.3 f 1.0 (4) NS 3.7k 1.2 (4)*" NS Pituitary Metubolism, Elsevier/North-Holland Biomedical Press, Amsterdam Testes 3.7? 1.6 (6) NS 5.7k2.3 (6)tC NS Tuman, R.W. & Doisy, R. J. (1977) Diabetes 26,82&826 Plasma 210?45(11) NS 375?120(5) NS Underwood, E. J. (1977) Trace Elements in Human and Animal Urine 705 k 110 (10) 2 . 8 ~ 410-t 155 ( 5 ) NS Nutrition, 4th edn., Academic Press, London PETER R. FLATT* and PER-OLOF BERGGRENt *Division of Nutrition and Food Science, Department of Biochemistry, University of Surrey, Guildford, Surrey GU2 S X H , U.K., and ?Department of Medical Cell Biology. University of Uppsala, Uppsala S-751 23, Sweden
1983
