Biomedical subjects

F R Dunshea

Publications and source records attributed to F R Dunshea.

At least 37 records · Page 2Linked to original sources

PubMed1997

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↗

PubMed1997

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↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1994

Pregnancy but not moderate undernutrition attenuates insulin suppression of fat mobilization in sheep.

Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Plasma concentrations of nonesterified fatty acids (NEFA) and glycerol were measured under basal conditions and during infusion of various doses of insulin while maintaining euglycemia (hyperinsulinemic, euglycemic clamp technique). Pregnancy and undernutrition separately increased basal plasma NEFA concentration in an additive manner; plasma glycerol was increased by pregnancy but unaffected by undernutrition. The molar ratio of NEFA to glycerol was significantly greater in underfed ewes. Analysis of dose-response relations between plasma insulin and metabolites during insulin infusions showed that maximally insulin-suppressed concentrations of NEFA and glycerol were significantly greater in pregnant than in nonpregnant ewes but were unaffected by undernutrition. Neither pregnancy nor undernutrition affected the maximally insulin-suppressed NEFA to glycerol ratio, or the plasma insulin concentration for 50% maximal responses to insulin of plasma NEFA, plasma glycerol, or the plasma NEFA to glycerol ratio. Thus, even in ewes at or close to zero energy balance, pregnancy seems to reduce adipose responsiveness but not sensitivity to the antilipolytic effect of insulin. This is another manifestation of the normal development of insulin resistance in maternal tissues during late pregnancy.

Animal Nutritional Physiological Phenomena↗

PubMed1994

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↗

PubMed1993

Evaluation of the arteriovenous difference technique to simultaneously estimate protein synthesis and degradation in the hindlimb of fed and chronically underfed steers.

Our objectives were to validate a technique to measure protein turnover based on net fluxes of tyrosine radioactivity and mass across the hindlimb, and to describe the impact of nutrition on hindlimb protein kinetics and nutrient utilization in growing Holstein steers. External iliac vessels were catheterized to allow for measurements of hindlimb arteriovenous (AV) differences and blood flow. Animals were used in a single reversal design with 16-d periods. Treatments were either 60% (0.6M) or 220% (2.2M) of the energy required for maintenance. On d 12 and 14 of each period, a primed-continuous infusion of L-[side chain-2,3-3H]tyrosine was initiated, followed by a 4-h sampling period to assess hindlimb nutrient utilization and protein kinetics. Well-fed steers exhibited rates of hindlimb utilization for non-nitrogenous energy substrates and amino acids that were consistent with values previously reported for well-fed ruminants. Underfeeding decreased hindlimb blood flow (62%), oxygen consumption (51%) and utilization of respiratory fuels (64-73%). Protein synthesis was also reduced (49%), leading to net nitrogen loss from the hindlimb. The estimated energy cost of protein synthesis accounted for 13% of hindlimb oxygen consumption across intake levels. Hindlimb protein balance was consistent with whole-body balance, adding credence to derived rates of degradation. Overall, data support the validity of the AV difference technique to estimate components of hindlimb protein turnover.

Animals↗

PubMed1993

Pregnancy and undernutrition alter glucose metabolic responses to insulin in sheep.

Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED50) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (Rmax) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither Rmax nor ED50 for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.

Animals↗

PubMed1993

Interrelationships between sex and ractopamine on protein and lipid deposition in rapidly growing pigs.

Sixty pigs were used to investigate the effects of two levels of dietary ractopamine (RAC; 0 and 20 mg/kg) and three sex types (SEX; boars, gilts, and barrows) on performance over the live weight range 60 to 90 kg. Pigs were housed in individual pens and allowed ad libitum access to a diet containing 3.466 Mcal of DE and 10.7 g of lysine/kg. Control boars exhibited faster and more efficient growth and deposited more protein and less fat than gilts or barrows. The RAC increased ADG by 17 and 21% in gilts and barrows but not in boars. Feed intake was not altered by dietary RAC. Dietary RAC increased the rate of protein deposition by 15, 42, and 41% in boars, gilts, and barrows, respectively. Nevertheless, the daily rate of protein deposition was greatest in RAC-treated boars. The RAC tended to reduce the daily rate of fat deposition by 21% in boars but not in gilts or barrows. Carcass protein content increased by 5% and fat content decreased by 8% in response to RAC. These improvements in carcass composition occurred without compromising meat quality. Results show that RAC is a potent stimulator of protein deposition in finishing pigs. However, increased protein deposition is not necessarily at the expense of fat deposition.

Adipose Tissue↗

PubMed1993

Interrelationships between dietary protein and ractopamine on protein and lipid deposition in finishing gilts.

Fifty-two gilts were used to investigate the effects of two levels of dietary ractopamine (RAC; 0 and 20 mg/kg) and six levels of dietary protein content (DPC; 8.5, 11.2, 14.0, 16.7, 19.5, and 22.2%) on performance over the live weight range from 60 to 90 kg. Pigs were housed in individual pens and restrictively fed their treatment diets according to a sliding scale related to live weight (average intake approximately 7.0 Mcal of DE/d). The ADG increased with increasing DPC for both control and RAC-treated gilts. The RAC further increased ADG at DPC > 14%; improvements were most apparent during the first 3 to 4 wk. There was a significant linear interaction between DPC and RAC for average daily carcass gain. Although carcass gain was not affected by RAC at the three lowest DPC, it was significantly increased for the three highest DPC. Feed to gain decreased with increasing DPC in a similar manner for both control and RAC-treated gilts. The relationship between empty body protein deposition and DPC could be described by a quadratic and rectilinear model. Regardless of the model employed, protein deposition increased with DPC at the same rate for both the control and RAC-treated gilts over at least the two lowest levels of DPC (< 11.2%). At higher DPC maximal rates of protein deposition were at least 21% greater in RAC-treated gilts; these rates were achieved at 3% higher DPC for RAC-treated gilts. Fat deposition decreased with increasing DPC but was unchanged by dietary RAC. Because the biological efficiency of protein use was unchanged, RAC-treated gilts have greater dietary protein requirements than controls do.

Adipose Tissue↗

PubMed1993

Effect of in vivo somatotropin treatment of growing pigs on adipose tissue lipogenesis.

The present study was undertaken to determine the effects of porcine somatotropin (pST) on glucose flux rates, lipogenic enzyme activities, and the abundance of fatty acid synthase mRNA in pig adipose tissue. Barrows were injected daily with 120 micrograms of pST/kg BW (n = 6) or excipient (n = 6). On d 11 of treatment, pigs were slaughtered (empty BW = 77 +/- 2 kg) and subcutaneous adipose tissue was collected. Basal incorporation of [14C]glucose into total lipid decreased by 86% with pST treatment, whereas glucose oxidation to CO2 decreased by 79%. Insulin (10 ng/mL) stimulated both glucose oxidation and incorporation into lipid by a small increment of similar magnitude for both treatment groups. Rates of lipogenesis determined in vitro were highly correlated with similar measurements made in vivo on the same set of animals (r = .76). The reduction in basal rates of lipogenesis corresponded to a 79% decrease in total (activated) acetyl-coenzyme A carboxylase activity and a 67% decrease in fatty acid synthase activity. Reduced nicotinamide adenine dinucleotide phosphate-generating enzymes were decreased to a lesser extent. Northern blot analysis of RNA from the same animals reveal a 90% decrease in mRNA for fatty acid synthase in the pST-treated group. The correlation between mRNA abundance and enzyme activity for fatty acid synthase was .90. These data indicate that the pST-induced reduction in adipose tissue lipid accretion in growing barrows is largely a result of diminished rates of lipogenesis that are manifestations of the decreased activities of the fatty acid-synthesizing enzymes. These changes seem to result from suppression of genes that encode for the lipogenic enzymes.

Acetyl-CoA Carboxylase↗

PubMed1993

Effect of metabolism modifiers on lipid metabolism in the pig.

Porcine somatotropin (pST) and certain beta-adrenergic agonists are potent metabolic modifiers that can improve performance in pigs. Pigs treated with either compounds utilize feed more efficiently and are leaner than controls. Comparative slaughter data clearly demonstrate that pST and some beta-agonists stimulate protein deposition. Porcine somatotropin decreases lipid deposition, but this is not the case for all beta-agonists. Somatotropin decreases lipid deposition through decreasing adipose tissue sensitivity to insulin, inhibiting lipogenesis, and perhaps stimulating lipolysis. Although lipolysis is increased during pST treatment of growing pigs, the greatest consequence is decreased lipogenesis. Although under controlled conditions certain beta-agonists stimulate lipolysis and inhibit lipogenesis, the limited metabolic studies suggest that at doses that are most efficacious for enhanced protein deposition, there are limited effects on lipid metabolism. In part, this may be due to desensitization of adipose tissue beta-adrenergic receptors and possibly a consequence of antagonism of beta-receptors.

Adrenergic beta-Agonists↗

PubMed1992

Temporal response of circulating metabolites and hormones during somatotropin treatment of growing pigs.

Temporal responses in the circulating concentrations of a number of intermediary metabolites and metabolic hormones were studied in chronically catheterized barrows (n = 4 per treatment) after either daily i.m. injection of porcine somatotropin (pST, 120 micrograms/kg of BW) or excipient. Blood sampling (every 1 or 2 h) began 24 h before the first injection (d 0) and continued until the end of d 2. Sampling was repeated on d 7 of treatment. Feed intake declined by d 3 in the pST-treated pigs and was 31% lower by d 7 of treatment (P less than .05). Blood glucose and plasma insulin concentrations began to increase about 3 h after the first pST injection, almost returning to preinjection levels before the next injection. By the end of d 2, circulating levels of glucose and insulin were higher in pST-treated pigs than in the controls. A temporal pattern of hyperglycemia and hyperinsulinemia was observed postinjection on each day of treatment. Although pST treatment did not chronically increase basal plasma concentrations of nonesterified fatty acids and glycerol, both metabolites exhibited transient postinjection elevations, the magnitudes of which were augmented by duration of treatment. Plasma urea nitrogen concentrations began to decrease within a few hours after the first pST injection and by d 7 were 70% (P less than .01) lower in the pST-treated pigs. A model is presented implicating pST-induced decreases in peripheral tissue insulin sensitivity and(or) responsiveness in the observed temporal responses in lipid and carbohydrate metabolism.

Animals↗

PubMed1992

Effect of somatotropin on nonesterified fatty acid and glycerol metabolism in growing pigs.

Eight crossbred barrows (71 kg initial BW) were allocated to two treatments involving daily i.m. injections of either excipient (control) or recombinantly derived porcine somatotropin (120 micrograms/kg of BW). On d 8 of treatment, beginning 15 h after injection, glycerol and nonesterified fatty acid (NEFA) kinetics were determined using a primed, continuous infusion of [2-3H]glycerol and [9,10(n)-3H]oleic acid. Kinetics were examined under both basal conditions and during a hyperinsulinemic/euglycemic clamp. Plasma concentrations of NEFA and glycerol and their respective entry rates were highly correlated. Insulin had no effect on plasma glycerol or glycerol entry rate, probably due to the very low rates that were observed in both the control and somatotropin-treated pigs. However, both plasma NEFA and oleic acid entry rate were reduced during hyperinsulinemia. Although indices of fat mobilization tended to be higher in pigs treated with somatotropin, the magnitude of the increases were small and would be sufficient to account for only a minor fraction of the decreased lipid accretion observed in somatotropin-treated pigs.

Animals↗