B W Gallaher

Metabolic consequences of intrauterine growth retardation

This review focuses on intrauterine growth retardation (IUGR) occurring spontaneously and without a defined infective, toxic or genetic cause. Such fetal growth retardation is generally thought to be a consequence of inadequate provision of nutritional substrates across the placenta.

Growth hormone treatment of breeding bulls used for artificial insemination improves fertilization rates

To evaluate new therapeutical concepts for male subfertility, we tested the effects of exogenous recombinant bovine growth hormone (rbGH) on various endocrine and metabolic parameters both in blood and in seminal plasma of bulls. Sperm quality was assessed morphometrically and by monitoring the number of successful artificial inseminations (AIs) defined as non-return rates (NRR). Aliquots of 450 semen samples were used from each bull and each experimental period (4 wk before, 14 weeks during and 6 wk after treatment). Six out of ten sires (average age 8.4 years) were treated every two weeks with 640-mg depot formulated rbGH (Eli Lilly). Four bulls received vehicle only. Blood plasma bGH, IGF-I, insulin and glucose concentrations were increased with rbGH treatment. In seminal plasma there was no effect of rbGH treatment on fructose and citrate or on testosterone concentrations. With one exception, rbGH-treated bulls had greater IGFBP-3 concentrations in seminal plasma. Motility of spermatozoa after freezing and thawing was increased compared with pretreatment rates. Most interestingly, the number of successful AIs was increased by an average of 6.0% NRR when ejaculates from rbGH-treated bulls were used.

Periconceptual undernutrition resets plasma IGFBP levels and alters the response of IGFBP-1, IGFBP-3 and IGF-1 to subsequent maternal undernutrition in fetal sheep

Maternal undernutrition inhibits fetal growth and alters circulating levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs). This study investigates whether the fetal IGF axis could be reprogrammed by maternal undernutrition and hence be a potential contributing factor to changes in fetal and postnatal metabolism. Ewes were either fed a lib. or undernourished from day-60 to day 30 of gestation, and then both groups were fed ad lib. These groups were further divided at day 105, either being fed ad lib or undernourished until day 115. Fetal blood samples were obtained at day 105 and day 115. IGFBP-1 and IGFBP-3 levels were lower at day 105 in the periconceptually undernourished fetuses. Levels of IGFBP-1 were increased and IGFBP-3, IGFBP-4, IGF-1, glucose and insulin were reduced at day 115 after undernutrition. The degree of change in IGFBP-1, IGFBP-3 and IGF-I between day 105 and day 115 was greater in fetuses receiving low periconceptual nutrition. These results indicate that periconceptual undernutrition is able to reprogramme the fetal IGF axis such that the responses of IGF-I and the IGFBPs to undernutrition in late gestation are markedly altered.

The circulating molecular weight forms of infused recombinant insulin-like growth factor-I and effects on glucose and fat metabolism in lambs

SummaryWe have investigated the relationship between the plasma distribution of infused recominant insulin-like growth factor-I across the insulin-like growth factor binding proteins and the resultant effects on glucose and fat metabolism. The studies were performed in 24-h fasted ram lambs which received primed constant infusions of 3H labelled glucose tracer. When isotopic equilibrium had been reached, the animals received 90-min infusions of human insulin-like growth factor-I at various doses (2.5, 20, 40 and 120 μg· kg−1·h−1, n=3 for each dose). Total plasma insulin-like growth factor-I was significantly elevated by infusion at a rate of 40 μg·kg−1·h−1 (from 185±14 μg/l to 442±41 μg/l, p<0.05) and 120μg·kg−1h−1 (from 181±2 μg/l to 953±39 μg/1, p<0.005). The plasma concentrations of insulin-like growth factor-I not associated with binding proteins remained undetectable (<15 μg/l) at the end of the 2.5 and 20 μg·kg−1·h−1 doses, but were significantly elevated at the end of the 40 and 120 μg·kg−1·h−1 infusions (to 71±14 μg/l, p<0.05 and 176±55 μg/l, p<0.01 respectively). The infused insulin-like growth factor-I associated primarily with 35–60 kilodalton binding proteins. Glucose kinetics were significantly altered only by the highest dose infusion, during which there was a fall in plasma glucose concentration from 3.5±0.2 mmol/l to 1.9±0.2 mmol/l (p<0.05). This was due to a 51% increase in the rate of glucose clearance. There was no significant change in the rate of glucose production. The plasma concentrations of glycerol and non-esterified fatty acid were not changed by any of the doses infused. We conclude that the hypoglycaemic action of infused recombinant insulin-like growth factor-I relates to a marked elevation of free insulin-like growth factor-I in the plasma, but that a threshold concentration of free insulin-like growth factor-I must be exceeded before this action is observed. The hypoglycaemic action of recominant insulin-like growth factor-I results primarily from an increase in glucose clearance while glucose metabolism was more sensitive than fat metabolism to infused recominant insulin-like growth factor-I. Both these actions contrast with those of insulin, and suggest that the acute metabolic effects of recombinant insulin-like growth factor-I are not mediated simply by cross-reaction with insulin receptors.

Bioavailability of calcium is equivalent from milk fortified with either calcium carbonate or milk calcium in growing male rats

Absorbability of calcium from milk and a variety of calcium salts has been a significant focus of studies over recent years. The present study compared the bioavailability of calcium from skim milk fortified with calcium carbonate or milk calcium, using young growing male rats. Primary outcomes were bone mineral density, bone calcium content, bone breaking strength and urinary excretion of collagen cross-links, a measure of bone resorption. Results showed that there was no significant difference in any of the measured parameters. The implication is that the kind of calcium salt used for fortification is not the determining factor for bioavailability. This agrees with various human studies, which have shown that different salts are absorbed to similar extents. Calcium fortified food products or milk is a convenient option to increase dietary calcium intake.