Environmental factors are important in the aetiology of glucose intolerance, type II diabetes and IHD. The lack of vitamin D, which is necessary for adequate insulin secretion, relates demographically to increased risk of myocardial infarction. These disorders are connected, degenerative vascular disease increasing with glucose intolerance and diabetes and, with its risk factors, comprising syndrome ‘X’. Evidence is presented suggesting that vitamin D deficiency may be an avoidable risk factor for syndrome ‘X’, adding another preventative measure to current recommendations which are aimed at reducing the worldwide epidemic of these disorders. Experimentally, vitamin D deficiency progressively reduces insulin secretion; glucose intolerance follows and becomes irreversible. Relationships between vitamin D status, glucose tolerance and 30 min insulin secretion during oral glucose tolerance tests are reported in British Asians; insulin secretion, but not glycaemia, improving with short-term supplementation. Studies showing reduction in blood pressure and in risk of heart attack and diabetes with exercise (usually outdoor), rarely consider the role of vitamin D status. Glycaemia and insulin secretion in elderly European men, however, relate to vitamin D status, independent of season or physical activity. Prolonged supplementation can improve glycaemia. Hypertension improves with vitamin D treatment with or without initial deficiency. Vitamin D status and climate are reviewed as risk factors for myocardial infarction; the risk reducing with altitude despite increasing cold. Glycaemia and fibrinogenaemia improve and insulin secretion increases in summer. Variation in vitamin D requirements could arise from genetic differences in vitamin D processing since bone density can vary with vitamin D-receptor genotype. Vitamin D receptors are present in islet β cells and we report insulin secretion in healthy Asians differing profoundly with the Apa I genotype, being independent of vitamin D status. Those at risk of vitamin D deficiency include the elderly, those living indoors or having a covered-up style of dress, especially dark-skinned immigrants, and pregnant women, and these are groups recognized as being at increased risk of diabetes.

Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTM-treated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3·4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, testes and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0·02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0·02) and retained in the cerebellum and medulla oblongata in the TTM-treated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a strongly positive correlation (r 0·7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification.

A lower BMR of Indians, when compared with Westerners matched for age, sex, and either surface area or body weight, has often been reported in the literature and has been interpreted to reflect an ethnic influence on BMR. To determine the contribution of body composition to these observed differences in BMR, we analysed the data on ninety-six Indians and eighty-one Caucasian Australians of both sexes, aged 18–30 years, studied in Bangalore, India and Melbourne, Australia. Absolute BMR and BMR adjusted for body weight were significantly lower in Indians when compared with Australians of the corresponding sex. However, BMR adjusted for fat-free mass (FFM) in men, and BMR adjusted for FFM and fat mass (FM) in women, were not significantly different between the two groups. Stepwise regression of FFM, FM, sex (0 = women; 1 = men) and ethnicity (0 = Indian; 1 = Australian) on BMR, resulted in the following relationship for the combined data on all subjects: BMR=88.7 × FFM (kg) + 1713 (n 177; r 0.92; r2 0.85; see 425 kJ). The Indian equations of Hayter & Henry (1994), based on body weight, resulted in a significant bias (measured – predicted BMR) of 318 (SE 54) kJ/d in Indian men and -409 (SE 70) kJ/d in Indian women. The equation of Cunningham (1991), based on FFM, accurately predicted the BMR of Indian men, Indian women and Australian men. The small but significant bias of 185 (SE 61)kJ/d in Australian women, may be explained by the significant contribution of FM to BMR in this group. The present study does not provide any evidence for an ethnic influence on basal metabolism. The results strongly support the use of FFM, rather than body weight, for the prediction of BMR in population groups of varying body size and composition. This would allow an accurate estimation of BMR and hence energy requirements in population groups worldwide.

To investigate the effect of a low (80 mmol/d) or high (180 mmol/d) Na intake for 14 d on biochemical markers of bone turnover in Na-sensitive and Na-non-sensitive healthy young women, twenty-nine subjects were screened for responsiveness of urinary Ca excretion to increasing dietary Na intake (40, 80, 120 and 200mmol/d for 7d). In a crossover study, the eight Na-sensitive and eight of the twenty-one Na-non-sensitive subjects were randomly assigned to diets containing either 80 or 180 mmol Na/d for 14 d followed by crossover to the alternative diet for a further 14 d. Dietary Ca was restricted to 12.5mmol/d throughout. During each dietary period, fasting morning first void urine samples (last 3 d) and fasting blood serum samples (morning of twelfth day) were collected. Increasing Na intake from 80 to 180 mmol/d increased urinary Na about twofold in both the Na-sensitive and Na-non-sensitive groups and increased urinary Ca excretion (by 73%) in the Na-sensitive group only. Biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline) and bone formation (serum osteocalcin and bone-specific alkaline phosphatase; EC 3.1.3.1) were unaffected by increasing dietary Na in either group. It is concluded that the Na-induced calciuria observed in the Na-sensitive healthy young women did not result in increased bone resorption or turnover and, despite restricted Ca intake, adaptation of dietary Ca absorption may have compensated for the increased urinary Ca loss.

From days 4–104 of pregnancy, adolescent sheep, weighing 43·7 (SE 0·87)kg were offered a complete diet at two different intakes (approximately 5 or 15 kg/week) designed to meet slightly, or well above, maternal maintenance requirements. The fetal and maternal muscles were taken on day 104 of pregnancy and analysed for total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal weight gain, weighed more (76·5 (SE 4·5) v. 50·0 (SE 1·7) kg) and had muscles with a greater fresh weight, whilst their fetuses had smaller muscles, than those fed at a lower intake. Plantaris muscle of the ewes fed at the high intake contained more RNA and protein; again the opposite situation was found in the fetal muscle. On the higher maternal intakes, the DNA, RNA and protein contents of the fetal plantaris muscle were less than in fetuses of ewes fed at the lower intake. To investigate the possible mechanisms involved in this decrease in fetal muscle mass, cytosolic and membrane-associated muscle proteins were subjected to Western immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a family of enzymes known to play an important role in cell growth. Five PKC isoforms (α, ε, θ, μ and ζ) were identified in fetal muscle. One of these, PKC-α, was located predominantly in the cytosolic compartment in the smaller fetuses of the ewes fed at a high plane of nutrition, but was present to a greater extent in the membranes of the more rapidly growing fetuses of the ewes fed at the lower intake. This was the only isoform to demonstrate nutritionally related changes in its subcellular compartmentation suggesting that it may mediate some aspects of the change in fetal growth rate.

We investigated the influence of restricted maternal nutrition between 30 and 80 d gestation on placental growth. Singleton-bearing ewes were fed on either 0.6 (i.e. nutrient restricted) times their energy requirements or 2.25 times this amount (i.e. controls) up to 80 d gestation, when their placentas and fetuses were sampled and analysed. Nutrient-restricted ewes lost body condition score but not body weight and had lower plasma thyroid hormone concentrations than controls, but there were no differences in plasma glucose, non-esterified fatty acids or 3-hydroxybutyrate concentrations between groups. There was no effect of maternal nutrient restriction on fetal weight, conformation or organ weights with the exception of brain weight which was lower in nutrient-restricted ewes. Nutrient restriction had no effect on total placental weight, or proportion of inverted placentomes, but was associated with an increased abundance of small placentomes and decreased weight of the fetal but not maternal components of the placenta. Fetal cotyledons from nutrient-restricted ewes also had a lower DNA but higher haemoglobin concentration than those sampled from controls. The plasma concentration of triiodothyronine in umbilical cord plasma was also increased in fetuses from nutrient-restricted ewes. In conclusion, maternal nutrient restriction during early-mid gestation is associated with a smaller placenta.

The activities of the two key enzymes involved in glutamine metabolism, glutaminase (EC 3.5.1.2) and glutamine synthetase (EC 6.3.1.2), have been measured in the various tissues of the gastrointestinal (GI) tract of the rat, from the mouth to the rectum. Glutaminase activity was particularly high in the mucosa of the small intestine, where its activity accounted for more than 80% of the total activity of the GI tract. In contrast, the mouth and oesophagus had very low activities, accounting for less than 2% of the total. Glutamine synthetase was mainly confined to the lower part of the stomach, which accounted for almost 90% of the total activity of the GI tract. Activity in the small intestine was very low, accounting for less than 2% of the total, and similarly low levels were found in the mouth and oesophagus. The data provide the most complete information on the distribution of these enzymes in the GI tract of the rat and suggest: (a) that the mucosa of the small intestine has the highest capacity for glutamine breakdown but the lowest capacity for its synthesis, and so requires an external source of this amino acid; (b) that there is little potential for glutamine synthesis or breakdown in the mouth and oesophagus; and (c) that the lower stomach has a substantial capacity to synthesize glutamine, in contrast to the rest of the GI tract. The results of the investigation are relevant to sites of glutamine metabolism in therapeutic studies involving glutamine administration discussed with reference to reports of the effects of glutamine administration on GI tract injury.

Three experiments were carried out to establish a response model between intake and urinary excretion of purine compounds. In Expt 1 the relationship between the intake of purine bases (PB) and the excretion of total purine derivatives (PD) was determined in seven growing rabbits with a mean initial live weight (LW) of 2·03 (SE 0·185) kg, aged 70 d, each fitted with a wooden neck collar to prevent caecotrophagy. They were fed on five experimental diets formulated with different levels of nucleic acids (0·00, 3·75, 7·50, 11·25, 15·00 g yeast-RNA/kg diet). The relationship between intake of purine (x, μmol/kg W0·75) and total urinary PD excretion (y, μmol/kg W0·75), y = 0·56 + 0·67x (r2 0·86; RSD 0·338), indicated that about 70% of duodenal PB were recovered as urinary PD and that the endogenous contribution was constant and independent of dietary PB supply. Endogenous excretion of PD (allantoin and uric acid) was measured in a second experiment using six rabbits fed on a purine-free diet and fitted with neck collars to avoid caecotrophagy. Basal daily urinary excretion values for allantoin and uric acid were 532 (SE 33·9) and 55 (SE 7·3) μmol/kg W0·75 respectively; xanthine and hypoxanthine were not found in urine samples and therefore the sum of allantoin and uric acid should comprise the total excretion of PD (588 (SE 40·1) μmol/kg W0·75). The xanthine oxidase (EC 1·2.3·2) activity in plasma, liver, duodenum, jejunum and kidney was measured in a third experiment. The activities of xanthine oxidase in duodenal and jejunal mucosa, liver and kidney were: 0·61 (SE 0·095), 0·37 (SE 0·045), 0·035 (SE 0·001) and 0 units/g fresh tissue respectively and in plasma 2·96 (SE 0·094) units/1. The results show that urinary excretion of PD may be a useful tool to estimate duodenal PB input and microbial protein intake once the relationship between PB and N has been established in caecal micro-organisms.

To reassess the hypothesis that fatty acid catabolism occurs to completion via β-oxidation, male Sprague–Dawley rats receiving continuous total parenteral nutrition (TPN) including 43% energy as fat were infused with [1-13C]- or [8-13C]triolein. Expired CO2 was collected continuously for 4 h and its 13C: 12C ratio determined by isotope–ratio mass spectrometry. Bicarbonate retention was also assessed over 4 h by infusion of NaH14CO3 and measurement of the expired 14CO2. A possible loss of label from [8-13C]oleic acid from the citric acid cycle via labelled acetyl-CoA without oxidation to CO2 was assessed by infusing further animals with acetate labelled with 14C either at C atoms 1 or 2 and determination of its conversion to expired 14CO2. At isotopic steady state, 63.2 (SE 1.6)% (n 8) of the infused [1-14C]acetate and 46.0 (SE 1.2)% (n 8) of [2-14C]acetate was recovered as expired 14CO2. After correction for bicarbonate retention and non-oxidative isotope loss, 37.3 (SE 1.2)% (n 20) of the [1-13C]triolein was found to have been oxidized, whereas 32.6 (SE 1.0)% (n 20) of the [8-13C]triolein was oxidized (P ≤ 0.01). The lower oxidation of the C atom at position 8 of oleic acid than that at position 1 indicates incomplete oxidative breakdown of the fatty acid after entering β-oxidation.