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F R Dunshea

Publications and source records attributed to F R Dunshea.

At least 19 recordsLinked to original sources

Long-term alterations in adiposity affect the expression of melanin-concentrating hormone and enkephalin but not proopiomelanocortin in the hypothalamus of ovariectomized ewes.

We have developed a ruminant model to study long-term alterations in adiposity on the expression of appetite-regulating peptides in the hypothalamus. In this model endocrine and metabolic status are fully defined as well as body composition. The current study sought to define the effects of altered adiposity on the expression of genes for neuropeptide Y (NPY), POMC, enkephalin (ENK), and melanin-concentrating hormone (MCH). Ovariectomized ewes with high (60 +/- 1 kg) (FAT) or low (37 +/- 3 kg) body weights (THIN) were blood sampled every 10 min for 8 h to determine metabolic and endocrine status. The animals were then killed and the brains perfused for in situ hybridization. Body composition analysis was performed on the carcass using dual energy x-ray absorptiometry; this indicated that the FAT animals were 36 +/- 1% fat, whereas the THIN animals were 15 +/- 2% fat. The LH interpulse interval was lower and mean GH concentrations were higher in the THIN animals; cortisol and TSH levels were not different between the two groups but free T4 and free T3 levels were lower; the FT3:FT4 ratio was higher in THIN ewes. Levels of insulin, lactate, and nonesterified fatty acids were lower in the THIN group, and plasma glucose and urea concentrations were similar in THIN and FAT animals. Levels of gene expression of NPY and MCH were higher in THIN ewes. POMC expression was similar in the two groups. In the THIN animals, ENK expression was lower in the paraventricular and ventromedial nuclei but higher in the periventricular region. In conclusion, we have shown that alterations in adiposity influence the expression of appetite-regulating peptides in the absence of ovarian steroids. The appetite stimulators, NPY and MCH, appear to be involved in the metabolic response to altered adiposity, whereas ENK in the periventricular region may be linked to the secretion of GH and possibly LH. Our results suggest that altered expression of appetite- regulating peptides can be linked with the endocrine and metabolic adaptations that occur with long-term changes in adiposity.

Adipose Tissue↗

Moderate doses of porcine somatotropin do not increase plasma insulin-like growth factor-I (IGF-I) or IGF binding protein-3.

The growth rate of the young pig is generally much less than its potential and may be constrained by endocrine status as well as by nutrient intake. The aim of this study was to determine whether porcine somatotropin (pST) could increase growth in the nursing pig. Fourteen sows nursing litters of 6 (n = 7) or 12 (n = 7) piglets were utilized to establish a high and low plane of nutrition for sucking pigs. On Day 4 of lactation, the median two male pigs from each litter were randomly allocated to one of two doses of pST (0 or 60 micrograms/kg/d) until weaning on Day 31. Pigs were bled on Days 4, 13, 22, and 31 of lactation and the plasma was analyzed for insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein-3 (IGFBP-3). Pigs were weaned into conventional accommodation and further weighed on Days 63, 91, and 119. Pigs from litters of 6 grew more quickly and weighed 2.2 kg (P = 0.01) and 3.5 kg (P = 0.04) more than pigs from litters of 12 at 31 and 63 d of age, respectively. There was no effect of pST on preweaning growth of sucking pigs (261 vs. 258 g/d, P = 0.68), although growth rate increased in the final 3 d before weaning at 31 d (241 vs. 294 g/d, P = 0.01). IGFBP-3 was greater (1.09 vs. 0.78 micrograms/ml, P < 0.001), whereas IGF-I tended to be greater (206 vs. 176 ng/ml, P = 0.14), in pigs from the small litters. There was no effect of pST on plasma IGF-I (182 vs. 195 ng/ml, P = 0.454) or IGFBP-3 (0.93 vs. 0.94 microgram/ml, P = 0.85) concentrations. Plasma IGF-I and IGFBP-3 were highly correlated with the growth rate of nursing pigs (R = 0.638 and 0.756, respectively). There were no effects of pST (340 vs. 328 ng/ml, P = 0.48) or litter size (336 vs. 333 ng/ml, P = 0.88) on IGF-II. In conclusion, pST had no little or no effect on growth performance or plasma IGF-I, IGF-II, or IGFBP-3 in sucking pigs on either a high or low plane of nutrition.

Animals↗

Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs.

Conjugated linoleic acids (CLA) decrease the body fat content of rodents; the aim of this study was to determine whether dietary CLA altered carcass composition of pigs. Female Large White x Landrace pigs (n = 66) were used in this study. To obtain initial body composition, six pigs were slaughtered at 57 kg live weight, whereas the remaining pigs were allocated to one of six dietary treatments (0, 1.25, 2.5, 5.0, 7.5 and 10.0 g/kg CLA, containing 55% of CLA isomers). The diets, containing 14.3 MJ digestible energy (DE) and 9. 3 g available lysine per kg, were fed ad libitum for 8 wk. Dietary CLA had no significant effect on average daily gain (861 vs. 911 g/d for pigs fed diets with and without CLA, P = 0.15) or feed intake (2. 83 vs. 2.80 kg/d, P = 0.74). The gain to feed ratio was increased by dietary CLA by 6.3% (0.328 vs. 0.348, P = 0.009). Fat deposition decreased linearly (-8.2 +/- 2.09 g/d for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing inclusion of CLA. At the highest level of CLA inclusion, fat deposition was decreased by 88 g/d (-31%). Similarly, the ratio of fat to lean tissue deposition decreased linearly (-0.093 +/- 0.0216 for each gram per kilogram increase in CLA concentration; P < 0.001) with increasing dietary CLA. The carcass lean tissue deposition response to dietary CLA was quadratic in nature and was maximized (+25%) at 5. 0 g/kg dietary CLA. Overall, dietary CLA increased the gain to feed ratio and lean tissue deposition and decreased fat deposition in finisher pigs.

Adipose Tissue↗

Wheat bran affects the site of fermentation of resistant starch and luminal indexes related to colon cancer risk: a study in pigs.

BACKGROUND: Recent studies suggest that resistant starch (effective in producing butyrate and lowering possibly toxic ammonia) is rapidly fermented in the proximal colon; the distal colon especially would, however, benefit from these properties of resistant starch. AIMS: To determine whether wheat bran (a rich source of insoluble non-starch polysaccharides), known to hasten gastrointestinal transit, could carry resistant starch through to the distal colon and thus shift its site of fermentation. METHODS: Twenty four pigs were fed four human type diets: a control diet, or control diet supplemented with resistant starch, wheat bran, or both. Intestinal contents and faeces were collected after two weeks. RESULTS: Without wheat bran, resistant starch was rapidly fermented in the caecum and proximal colon. Supplementation with wheat bran inhibited the caecal fermentation of resistant starch, resulting in an almost twofold increase (from 12.9 (2.5) to 20.5 (2.1) g/day, p<0.05) in resistant starch being fermented between the proximal colon and faeces. This resulted in higher butyrate (133%, p<0.05) and lower ammonia (81%, p<0.05) concentrations in the distal colonic regions. CONCLUSIONS: Wheat bran can shift the fermentation of resistant starch further distally, thereby improving the luminal conditions in the distal colonic regions where tumours most commonly occur. Therefore, the combined consumption of resistant starch and insoluble non-starch polysaccharides may contribute to the dietary modulation of colon cancer risk.

Ammonia↗

Effect of growth hormone administration on IGF binding protein-3 mRNA levels in porcine tissues.

The effect of short-term GH treatment on steady-state insulin-like growth factor binding protein-3 (IGFBP-3) mRNA levels in liver, kidney, longissimus dorsi muscle, stomach and jejunum was examined in pigs. Ten female crossbred pigs were allocated to either saline or GH (70 microg/kg/day) treatment by subcutaneous injection for 4 days. They were allowed to feed ad libitum, and were weighed daily. At the end of the treatment period, the pigs were slaughtered and samples of liver, kidney, skeletal muscle, stomach and jejunum were collected and total RNA was extracted. Steady-state levels of IGFBP-3 mRNA were quantified by RNase protection assay and were compared with the level of IGF-I class 1 and class 2 transcripts. IGFBP-3 mRNA increased in response to GH in both liver and kidney, but not in the other tissues sampled. Hepatic IGF-I mRNA responded to short-term GH treatment with a fourfold increase in IGF-I class 1 mRNA and an eightfold increase in IGF-I class 2 mRNA, which was liver specific. IGF-I class 1 mRNA was not responsive to GH treatment in other tissues. The short-term nature of this treatment suggests that the increase in hepatic IGFBP-3 and IGF-I transcripts is a relatively early response to treatment with GH, and that the increase in plasma concentrations of IGFBP-3 in response to GH are derived from the liver, the kidney, or both.

Animals↗

The effects of post-weaning progestagen treatment (Regumate) of early-weaned primiparous sows on subsequent reproductive performance.

This study investigated the effects of feeding the orally active progestagen, altrenogest (Regumate) post-weaning on the subsequent reproductive performance of early weaned sows. Ninety (90) Large White/Landrace first parity sows were randomly assigned to three treatments. Treatment 1 (EW) and treatment 3 (CW) sows were weaned on day 12 and day 24 post-partum, respectively while treatment 2 sows (EW-R) were weaned on day 12 post-partum and received an individual daily dose of 20 mg of Regumate on days 13 to 24 post-partum inclusive. Each sow was mated naturally at least twice at the first post-weaning or post-treatment oestrus and slaughtered on days 25-28 of pregnancy to determine the number of corpora lutea and embryos. Regumate-to-oestrus and weaning-to-oestrus intervals were similar for EW-R and CW sows (6.2 vs. 5.6 days). However, both intervals were significantly shorter (P < 0.01) than the weaning-to-oestrus interval of EW sows (7.3 days). An excellent synchronization of oestrus was achieved with Regumate treatment with 97% of treated sows in oestrus within 7 days of Regumate withdrawal compared with 64% for EW sows (P < 0.01) and 87% for CW sows (P > 0.05). Treatment with Regumate resulted in a significant increase in ovulation rate (16.9 vs. 15.4 and 14.9 for treatments EW-R, EW and CW, respectively; P < 0.05) and a non-significant increase in early embryonic survival (77% vs. 68% vs. 68% for treatments EW-R, EW and CW, respectively; P > 0.05). These results indicate that Regumate feeding is a potential management tool to alleviate the diminished reproductive performance associated with early weaning regimes since it leads to successful control of oestrus, higher ovulation and embryo survival rates and thus a greater potential litter size.

Animals↗

Assessment of apparent ileal digestibility of amino acids and nitrogen in cottonseed and soyabean meals fed to pigs determined using ileal dissection under halothane anaesthesia or following carbon dioxide-stunning.

Two experiments were conducted to determine apparent ileal digestibility of amino acids (AIDAA) and nitrogen (AIDN) in cottonseed meal (CSM) and soyabean meal (SBM) fed to growing pigs. In the first experiment, twenty-four male pigs (37.3 (SE 2.7) kg) were individually penned and randomized to either CSM or SBM diets. The diets contained 40% of the protein meal (either CSM or SBM) in a wheat starch-sucrose (1:1, w/w) base containing vitamins and minerals, and Cr2O3 as an indigestible marker. Pigs were acclimated to the experimental diets over a 3 d period and on day 4 through to day 14 were offered 1800 g/d of the diet. Diets were offered in three meals/d from day 4 to day 11 and in eight meals/d from day 12 to day 13. After the eighth hourly-meal on day 14, twelve pigs were anaesthetized with halothane while the remaining twelve pigs were CO2-stunned and processed using commercial slaughter procedures. Ileal digesta were collected from a 1500 mm portion of the terminal ileum of each pig and subsequently analysed for amino acids, N, organic matter and Cr. Results indicated that AIDAA of CSM and SBM were lower when digesta were collected following CO2-stunning than when digesta were obtained under halothane anaesthesia. Consistently, AIDN in CSM (0.51 v. 0.56) and SBM (0.55 v. 0.71) were lower (P < 0.05) in CO2-stunned pigs than in halothane-anaesthetized pigs. Furthermore, when digesta collection was conducted under halothane anaesthesia, AIDN of CSM was lower (P < 0.001) than that of SBM. In the second experiment, six male pigs (45 (SE 2.6) kg) were fitted with T-piece cannulas implanted in the terminal ileum, housed individually in metabolism cages, and randomly allocated to either CSM or SBM diets in a single reversal arrangement. Ileal digesta were collected for AIDAA and AIDN determination. Although statistical comparisons could not be made between the two experiments, the AIDAA and AIDN data obtained via cannulated pigs were similar to those values obtained using the halothane-anaesthesia method. Overall, the CO2-stunning method is not recommended for studies of amino acid or nitrogen ileal digestibilities, but may be useful for the study of other dietary constituents.

Amino Acids↗

The effect of dietary magnesium aspartate supplementation on pork quality.

Large White x Landrace boars (n = 48) were used to determine the effect of dietary magnesium aspartate supplementation (MgAsp) on subsequent stress and meat quality indicators. Dietary MgAsp supplementation increased plasma magnesium levels compared with pigs fed the control diet. Pigs fed the MgAsp-supplemented diet had lower norepinephrine concentrations at slaughter than pigs fed the control diet. Pigs fed the MgAsp-supplemented and the control diet had similar glycogen concentrations in the longissimus thoracis (LT) and biceps femoris (BF) muscle, whereas pigs fed the MgAsp-supplemented diet had lower lactic acid in the LT and BF muscle compared to pigs fed the control diet. Negative handling of pigs before slaughter reduced muscle glycogen in the LT and the BF muscle and increased the lactic acid levels in the LT and BF muscle compared to when pigs were minimally handled at the abattoir. Comparison of meat quality traits indicates that MgAsp supplementation to pigs raised the muscle pH in the LT muscle at 40 min and 24 h after slaughter. Pigs that were fed the MgAsp-supplemented diet had lower percentage of drip loss, lower surface lightness L, and had no PSE carcasses compared to pigs fed the control diet. Also, pigs that were fed the control diet and negatively handled at the abattoir before slaughter had the highest percentage of drip loss and incidence of PSE compared to other treatment groups. The results indicate that dietary MgAsp supplementation to pigs can significantly improve ultimate meat quality and reduce the incidence of PSE meat.

Abattoirs↗

Paradoxical increases of circulating nonesterified fatty acids in somatotropin treated cattle undergoing mild disturbances.

Effects of various doses of bovine somatotropin (bST) on plasma concentrations of nonesterified fatty acids (NEFA) were studied in a 14-d Latin square with six Holstein heifers. Animals were given daily injections of excipient or bST at 12:00 p.m. and fed twice daily at 7:00 a.m. and 7:00 p.m. On Day 14, plasma NEFA remained low through the day except around the 7:00 p.m. feeding when they were substantially elevated. The elevation was significantly greater in bST-treated animals and corresponded to the excitement of the animals in anticipation of the evening feeding. To further investigate this phenomenon, a second experiment was conducted in which nine growing Holstein steers were fed hourly and received either daily intramuscular (i.m.) injection of excipient or bST (120 mg/kg BW) for 15 d in a crossover design. Daily profiles of NEFA were obtained under undisturbed conditions or concurrently with intensive handling. Although no elevations could be detected in any case in control animals, bST caused a substantial rise in NEFA concentration only when animals were subjected to intensive handling. This suggested that NEFA peaks noted in bST-treated heifers in the first experiment resulted from increased ability of adipose tissue to respond to adrenergic stimulation associated with the anticipation of feeding. Consistent with this hypothesis, plasma NEFA concentrations in bST-treated steers were increased to a greater extent during a challenge involving i.v. injection of epinephrine. This amplification of adipose tissue response by bST must be considered when conducting intensive studies. Even the minimal excitement associated with blood sampling can confound the results regarding lipid mobilization, and this may have contributed to the notion that ST is a lipolytic hormone.

Adipose Tissue↗

IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys.

The relative acute hypoglycaemic potencies of IGF-I and several variants of IGF-I which bind poorly to the IGF-I binding proteins (IGFBPs) have been examined in marmosets (Callithrix jacchus) and the pig. In the marmoset study, IGF-I and des(1-3)IGF-I were compared in anaesthetised and conscious animals in a range of bolus doses from 42 to 270 micrograms/kg body weight. In the pig study, IGF-I was compared with four variants, des(1-3)IGF-I long-IGF-I, R3IGF-I and long-R3IGF-I (LR3IGF-I), which show reduced affinity for the IGFBPs as well as with insulin. Doses in the pig were 20 and 50 micrograms/kg body weight for the IGFs and 3 micrograms/kg for insulin. In each study serial blood samples were taken from 30 min before to 4 h after the bolus injection. Plasma glucose levels were decreased in a dose-responsive manner with the pig more sensitive than either the conscious or anaesthetised marmoset (maximum lowering 4.8, 3.7 and 2.5 mmol/l respectively). The IGF variants were consistently 2- to 3-fold more potent than IGF-I in each animal for lowering of plasma glucose to the nadir, with the potency reflecting the relative affinities for binding to the IGFBPs and the IGF-I receptors. Thus, hypoglycaemic potency was in the order IGF-I < long-IGF-I < R3IGF-I approximately LR3IGF-I < des (1-3)IGF-I. Notably the variants suppressed plasma glucose levels over a much longer period than did IGF-I, the cumulative suppression over four hours showing an approximately 4- to 8-fold increase in the extent of hypoglycaemia. The prolonged suppression was not simply proportional to the hypoglycaemic nadir; at doses equipotent for glucose lowering, the cumulative hypoglycaemic effect for the variants in either species was about 2-fold that for IGF-I. The differential effect of the variants in the marmoset could not be accounted for by correlated changes in plasma insulin, IGF-I or IGFBP levels in plasma. Indirect effects via inhibition of glucagon, or direct effects via hepatic insulin receptors are postulated to account for the results. There was a dose-related reduction in plasma amino acids in the pig but, unlike the case for plasma glucose, only one analogue, LR3IGF-I was more potent than IGF-I. The response to LR3IGF-I was accentuated at the high dosage but on the basis of the other variants tested this effect could not be ascribed to either of the incorporated molecular variations. Despite their more rapid clearance from the circulation, variants of IGF-I which show lower affinity for binding to IGFBPs show proportionately superior potency for sustained hypoglycaemic action. Since our data were obtained in animal models of accepted relevance to humans these results point to the possible superior efficacy of the variants, especially des(1-3)IGF-I, over IGF-I for use as an adjunct to insulin treatment of hyperglycaemic conditions.

Amino Acids↗

Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs.

Growth hormone (GH) improves growth performance in the pig. Analogues of insulin-like growth factor-I (IGF-I) that bind poorly to IGF binding proteins (IGFBP) stimulate growth in the rat but, in contrast, inhibit growth in the pig. This study was designed to determine the effect of IGF peptides alone or in combination with porcine GH (pGH) on growth characteristics and plasma hormone concentrations in finisher pigs. A four-day infusion of Long [R3] IGF-I (LR3IGF-I; 180 micrograms/kg/day) decreased the average daily gain, food intake, and plasma IGFBP-3, IGF-I and insulin concentrations. The mean plasma GH concentration was decreased by 23% and the area under the GH peaks was reduced by 60%. Co-administration of pGH (30 micrograms/kg/day) with LR3IGF-I had no interactive effect on growth performance, and plasma insulin, IGFBP-3 and IGF-I concentrations remained suppressed. The area under the GH peaks was not restored with this combination treatment although mean plasma GH concentrations were elevated in all animals receiving pGH. Infusion of IGF-I (180 micrograms/kg/day) decreased plasma insulin and mean GH concentrations but had no significant effect on IGFBP-3 concentrations. Average daily gain and feed intake were not changed by IGF-I treatment. A combination of IGF-I and pGH injection (30 micrograms/kg/day) increased plasma IGFBP-3 concentrations but plasma insulin levels remained suppressed. Plasma glucose levels were unaffected by any treatment. The study demonstrates that both IGF-I and LR3IGF-I suppress plasma GH concentrations in finisher pigs. This, in turn, may be responsible for the reduction in the plasma concentration of IGF-I, IGFBP-3 and insulin seen in LR3IGF-I-treated animals. The decrease in these parameters may contribute to the inhibitory effect of LR3IGF-I on growth performance in the pig.

Animals↗

The testis is not the major source of circulating follistatin in the ram.

The aims of this study were to determine the plasma concentrations of follistatin in rams and to assess if the testis contributes to circulating follistatin and if there is uptake or production of follistatin by the head in rams. Catheters were inserted in the carotid artery, jugular vein and spermatic vein of intact rams during the non-breeding season (experiment 1; n = 5) and breeding season (experiment 2; n = 4). In experiment 1, blood samples were collected from 5 rams every 10 min for 4 h, commencing 20-60 min after surgery. After 2 h of sampling 1 microgram gonadotrophin-releasing hormone (GnRH) was injected intravenously. In experiment 2, blood samples were collected from 4 of the rams used in experiment 1 by venipuncture 30 and 15 min before surgery and every 15 min throughout surgery. Commencing 1 h after surgery, matched samples were taken from each of the vessels every 10 min for 4 h (1-4 h after surgery), then every hour for 20 h (4-24 h after surgery) and then every 10 min for 4 h (24-28 h after surgery). In both experiments, follistatin secretion was non-pulsatile and there were no significant differences between the concentrations of follistatin in any of the vessels. There was a significant (P < 0.05) increase in the concentrations of follistatin in each of the vessels throughout the 4 h of 10-min sampling in both experiments. In experiment 2 plasma concentrations of follistatin in the jugular vein were significantly (P < 0.05) lower before surgery than at other stages of the experiment. During the non-breeding season (experiment 1) the concentrations of follistatin in all vessels were about 2-fold higher (P < 0.001) than during the breeding season (experiment 2). Concentrations of follistatin were measured in the testicular tissue of the ram, bull, monkey and rat and were found to be 13.6, 2.1, 2.5, 0.8 ng/g testis respectively. In experiment 3, blood samples were collected every 15 min for 4 h from castrated rams (n = 6) in the absence of treatment with testosterone propionate (TP) and after 7 days of treatment with a physiological dose of TP during the breeding and non-breeding seasons. There was no effect of stage of breeding season or TP on the plasma concentrations of follistatin and these concentrations in the castrated rams were similar to the concentrations in the intact rams in experiment 2. In experiment 4, the function of Leydig cells was stimulated by administration of human chorionic gonadotrophin but this had no effect on plasma concentrations of follistatin. These experiments show that the concentrations of follistatin in the plasma of rams are measurable, that the testis is not the major contributor to circulating follistatin and that there is no significant uptake or production of follistatin by the head in rams. It appears that the contribution of the testis to circulating follistatin may vary with the stage of the breeding season, being greater during the non-breeding season than the breeding season. The gonadotrophins and testosterone do not appear to have a direct effect on the secretion of follistatin in rams. The increase in concentrations of circulating follistatin during surgery and more frequent blood sampling suggest a stress-related effect on the production of follistatin.

Animals↗

The effect of exogenous somatotropin on lactation performance of first-litter sows.

To determine the effect of exogenous porcine somatotropin (ST) on lactation performance of sows, 24 first-litter sows were injected daily at 0800 with either 10 mg of recombinant ST or an equivalent volume of buffer between d 8 and 39 of lactation. Litter size was standardized to six (n = 2), seven (n = 8), eight (n = 6), or 10 (n = 8) pigs within each pair of sows by fostering pigs within a few days after parturition. Milk yield and composition of sows given ST was similar at all stages of lactation to that of control sows. Combining treatment data revealed that the milk yield of sows was related linearly (P < .01) to litter size and was described with the following equation: MY = 1.03 (+/- .71) + .899 (+/- .102) LS (n = 24, r2 = .78), where MY is average milk yield (kilograms/day) of sows over 4 to 7, 11 to 14, 18 to 21, 25 to 32, and 32 to 39 d of lactation and LS is number of pigs in the litter. The body temperature of sows increased (P < .05) in response to administration of ST. Plasma IGF-I and glucose were increased (P < .05) by ST, but plasma urea concentrations were lower (P < .05) in ST-treated sows. Sows treated with ST lost more backfat (P < .05) during lactation, but neither voluntary feed intake nor body weight loss was significantly (P > .05) affected by ST. These data indicate that a 10-mg daily injection of ST from d 8 to 39 of lactation alters metabolism but does not increase milk production in lactating first-litter sows.

Analysis of Variance↗

In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness.

IGF-I analogues that bind poorly to IGFBPs are substantially more potent than IGF-I at stimulating growth in rats. However, rodents differ from other mammals because they contain only minimal circulating levels of IGF-II and they are poorly responsive to GH. In this report we review a series of experiments carried out in pigs, a species that is both GH responsive and has high blood concentrations of IGF-II. Intravenous bolus administration of IGFs to 55 kg pigs depressed blood glucose with the potency greatest for analogues such as des (1-3) IGF-I, R3IGF-I and Long R3IGF-I that showed the weakest binding to pig IGFBP-3, a similar efficacy pattern to that reported in the rat. Chronic subcutaneous administration of Long R3IGF-I, however, reduced growth rates, led to a depression in food intake and lowered concentrations of IGF-I, IGF-II and IGFBP-3. IGF-I itself depressed IGF-II concentrations and did not stimulate growth. Subcutaneous infusion of IGFs over a 3-day period, also in 55 kg pigs, demonstrated that analogues that bound least well to IGFBP-3 were the most effective at reducing the concentration of this binding protein, suggesting that the inhibition of growth was related to the depression of IGFBP-3. On the other hand, IGF-I and Long R3IGF-I increased growth rats in neonatal pigs, especially under conditions of reduced food intake. As these anabolic effects occur at a developmental stage where the animals are insensitive to GH in a manner analogous to the situation in rats, it is plausible that the feed-back inhibition of GH secretion explains the catabolic response to IGFs in older pigs.

Aging↗

Responses to homeostatic signals in ractopamine-treated pigs.

The beta-agonist ractopamine (RAC) promotes protein deposition with little effect on fat deposition in the pig. To assess whether the lack of effect on fat deposition was due to changes in response to homeostatic signals, eight crossbred gilts (73 kg body weight (BW)) with venous catheters were used to examine plasma metabolite and hormone concentrations before and after intravenous injections of insulin and the beta 2-agonist fenoterol during dietary RAC (0 or 20 mg/kg) treatment. Pigs received intravenous challenges of insulin (1 microgram/kg BW) on days 3, 9 and 23 and fenoterol (2 micrograms/kg BW) on days 4, 10 and 24 of treatment. RAC was then withdrawn from the diet and insulin and fenoterol challenges were repeated 6 and 7 d later respectively. Blood samples for the determination of metabolite and hormone concentrations were taken at -30, -20, -10, -1, 2.5, 5, 10, 20, 30, 45, 60 and 120 min relative to the challenges. Dietary RAC decreased basal plasma insulin concentrations but had no effect on plasma glucose or non-esterified fatty acids (NEFA). Hypoglycaemic responses to insulin were not affected by RAC while the anti-lipolytic effects of insulin tended to be augmented. Dietary RAC decreased the lipolytic response to fenoterol, this being evident after 4 d treatment. Hypoglycaemic response to fenoterol was not changed whereas the hyperinsulinaemic response to fenoterol was attenuated by dietary RAC. Previous treatment with RAC did not influence basal hormone and metabolite concentrations or responses to homeostatic signals during the withdrawal period. While these results suggest little change in glucose metabolism, the de-sensitization of adipose tissue beta-adrenergic receptors is consistent with the observations that dietary RAC has little effect on the rate of fat deposition in the growing pig.

Adipose Tissue↗

IGF feedback effects on growth hormone secretion in ewes: evidence for action at the pituitary but not the hypothalamic level.

The putative negative feedback effects of IGF-I and IGF-II on GH secretion were tested by intracerebroventricular (icv) and intrapituitary administration to sheep. Over two consecutive days, serial jugular blood samples were taken at 10 min intervals for 6 h from ewes (n = 3/group) fitted with indwelling stainless steel cannulae into the lateral or third cerebral ventricles. The sheep were injected (icv) with either vehicle or purified ovine IGF-I (2, 4 or 8 micrograms). IGF-I injection had no effect on plasma GH secretion. Serial blood samples were taken from a second group of nine ewes in which ovine or recombinant human (rh) IGF-I was infused (2.5 micrograms/h for 2 h) into the third ventricle; once again, IGF-I failed to affect the episodic pattern of GH secretion. Three ewes fitted with indwelling stainless steel cannulae placed in the anterior pituitary gland were consecutively infused with either ovine or rhIGF-I (2.5 micrograms/h for 2 h) or vehicle. Plasma GH concentrations were suppressed in 3/3 sheep from 1-1.5 h after the commencement of infusion and GH levels remained low for the remainder of the sampling period. In another group of five ewes synergistic effects of IGF-I and IGF-II on GH secretion were tested by icv infusion of rhIGF-I, rhIGF-II, or rhIGF-I+rhIGF-II (5 micrograms/h for 2 h) or vehicle (sterile 10 mM HCl/saline). Each sheep received each treatment in a randomised design. Infusion (icv) of IGF-I and IGF-II alone or in combination failed to alter GH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of bovine somatotropin and insulin on whole-body and hindlimb glucose metabolism in growing steers.

Six Holstein steers (245 kg initial BW) were surgically prepared with chronic catheters to allow measurement of blood flow and nutrient flux across the hindlimb. Steers were used in a single-reversal design with 16-d treatment periods of daily i.m. injection of either excipient (control) or recombinantly derived bovine somatotropin (120 micrograms/kg BW). On d 15 of each period, whole-body and hindlimb glucose metabolism were studied during a primed continuous infusion of [6(-3)H]glucose, under both basal conditions and during a hyperinsulinemic/euglycemic clamp. Somatotropin increased (P < .01) basal blood glucose and serum insulin by 7 and 150% respectively, with no change in glucose irreversible loss rate (ILR). There was no effect of somatotropin on hindlimb blood flow or oxygen consumption. In contrast, hindlimb lactate uptake (P < .02) and the ratio of glucose to oxygen uptake (P < .08) were reduced by somatotropin. Insulin infusion stimulated (P < .01) glucose ILR and inhibited (P < .02) endogenous glucose production to a lesser extent during somatotropin treatment. Basal plasma nonesterified fatty acid concentrations were increased (P < .01) during somatotropin treatment and decreased (P < .02) during insulin infusion. Insulin infusion increased hindlimb blood flow and glucose uptake to similar extents during both treatment periods. These data demonstrate that somatotropin treatment of growing steers decreases response of tissues to insulin (sensitivity in muscle, sensitivity, and responsiveness in liver and adipose tissue), thereby increasing glucose availability to other tissues.

Adipose Tissue↗

Nutrient utilization and protein turnover in the hindlimb of cattle treated with bovine somatotropin.

Our objectives were to assess the effects of chronic administration of recombinant bovine somatotropin (bST) on nutrient utilization and protein turnover in the hindlimb of growing Holstein steers. External iliac vessels were catheterized to allow for hindlimb measurements of arteriovenous differences and blood flow. Animals were used in a single-reversal design with 16-d treatment periods of daily intramuscular injection of either excipient or 120 micrograms/kg body wt of bST. On d 11 and 13 of each period, a primed-continuous infusion of L-[sidechain-2,3-3H]tyrosine was initiated, followed by a 4-h sampling period to assess hindlimb nutrient utilization and protein kinetics. Somatotropin did not alter blood flow or the consumption of acetate and oxygen across the hindlimb. In contrast, glucose uptake was reduced by 22% despite increases in arterial concentrations of glucose and insulin of 10 and 114%, respectively. Treatment with bST increased hindlimb protein accretion (estimated from net uptake of tyrosine) and whole-body N balance, each by approximately 40%. A modest increase (10%) in the absolute rate of protein synthesis seemed to account for the improved N retention in the hindlimb with no change in the rate of protein degradation. Thus, bST reduced the responses of the hindlimb to insulin, and a small alteration in protein synthesis was sufficient to explain substantial improvement in protein deposition.

Amino Acids↗