Effects of porcine growth hormone on glucose metabolism of pigs: II. Glucose tolerance, peripheral tissue insulin sensitivity and glucose kinetics

This study was conducted to determine whether the increase in serum glucose observed in pigs treated chronically with pGH is due to an increase in hepatic glucose output or to an impairment in glucose clearance. Barrows (n = 4 per treatment) were treated with pituitary derived pGH (ppGH), recombinant pGH analog (rpGH) or vehicle. Pigs were treated for 28 d by daily i.m. injections. Insulin tolerance and glucose tolerance tests (GTT) were performed on d 19 and 21, respectively, following treatment with pGH. Glucose turnover was quantified on d 28 using [6-3H]glucose. Chronically treating pigs with pGH resulted in a significant decrease (26%; P less than .05) in glucose clearance, as determined by the GTT. Glucose clearance was affected similarly by ppGH and rpGH. Intra-arterial glucose infusion markedly increased plasma insulin concentration in pGH-treated pigs. Peak plasma insulin response was 87% and 58%, respectively, higher (P less than .05) in ppGH- and rpGH-treated than in control pigs. Insulin infusion elicited a marked hypoglycemia in pigs; however, the extent and duration of hypoglycemia were significantly less in pGH-treated pigs (ppGH or rpGH). Glucose production rates were 23% higher (P = .085) in ppGH-treated than in control pigs. These results establish that the hyperglycemia induced by pGH is the result of an increase in hepatic glucose output and a concurrent impairment in glucose clearance.     

Chronic effects of recombinant porcine growth hormone on adrenal weight and activity in pigs

This study was conducted to examine serum cortisol concentrations and adrenal cortisol output in pigs treated chronically with recombinant pGH (rpGH) at a maximally effective anabolic dose. Recombinant pGH (140 micrograms/kg body weight) was administered daily to eight barrows for 77 d. At slaughter, adrenal glands were removed, weighed and sliced; slices of fresh adrenal tissue were incubated for 1 h in the presence or absence of ACTH. Recombinant pGH increased adrenal weight by 39%. This change was accompanied by an inversely proportional reduction of in vitro cortisol output per gram of tissue, with the net result that total cortisol output per adrenal per kilogram of BW was unaltered, as was cortisol output in the presence of ACTH. Serum cortisol concentrations were measured in 10 barrows fitted with femoral artery catheters and treated daily with 0 or 140 micrograms rpGH/kg BW for 8 d. Basal and ACTH-stimulated cortisol concentrations were not altered by rpGH treatment. These results do not support our earlier speculation that a pGH-dependent increase in adrenal weight is associated with a chronic increase in adrenal activity, but rather demonstrate that corticosteroid output is tightly regulated and remains constant despite a marked increase in the size of the adrenal glands.     

Effects of intravenous ghrelin injection on plasma growth hormone,insulin and glucose concentrations in calves at weaning

Ghrelin action, which stimulates growth hormone (GH) secretion, may alter during the weaning period in calves. Our objective was to compare the effects of intravenous ghrelin injection on plasma GH, insulin and glucose concentrations in calves around the weaning period. Four Holstein bull calves were fed whole milk and allowed free access to solid feeds, and weaned at 7 weeks of age. Measurements were performed at weeks 1, 2, 4, 6, 7, 9, 11 and 13, when calves were intravenously injected with ghrelin (1.0 μg/kg body weight (BW)) through a catheter, and jugular blood samples were obtained temporally relative to the injection time. Estimated digestible energy intake per metabolic BW transiently decreased at week 7 because of low solid intake immediately after weaning, and thereafter gradually increased. Plasma insulin and glucose concentrations were not affected by ghrelin injection at all ages. In contrast, plasma GH concentrations increased with ghrelin injection at all ages. The incremental area of GH at week 7 was greatest and significantly higher compared with weeks 2, 4, 6 and 9. This result suggests that nutrient insufficiency immediately after weaning enhances GH responsiveness to ghrelin.     

Influence of dietary protein and recombinant porcine somatotropin administration in young pigs: growth, body composition and hormone status

The influence of dietary protein and recombinant porcine somatotropin (rpST) administration on growth and body composition was investigated in barrows. Ten groups of six pigs starting at 30 kg were restrictively fed (approximately 80% of ad libitum) one of five diets containing 11, 15, 19, 23 or 27% protein. Diets contained skim milk (12%). Soybean meal diluted with cornstarch was used as the supplemental source of dietary protein. Diets were isocaloric (3.8 Mcal DE/kg) and all contained the same amount of lysine (18 to 20 g/kg). Thirty pigs were treated daily with rpST (100 micrograms/kg) by i.m. injection; the remaining pigs were treated with sterile diluent (control) for 42 d. Growth rate was greater in rpST-treated pigs at all levels of protein intake; however, the magnitude of the response to rpST treatment was lowest among pigs fed the diet containing 11% protein. Feed:gain ratio, backfat depth and carcass fat content were decreased in rpST-treated pigs compared to respective controls. Additionally, the concentration of carcass fat decreased concomitantly with an increase in dietary protein intake. Concentration of carcass protein increased linearly as dietary protein increased in control and rpST-treated pigs. In contrast, treatment with rpST was associated with an increased visceral mass; the concentration of protein and fat in the viscera was influenced by protein intake but not by rpST. These results, characterized by few treatment interactions, suggest that when energy intake is kept constant and appropriately fed pigs serve as controls, dietary protein and rpST influence growth and body composition by independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of gender and genotype on the response of growing pigs to exogenous administration of porcine growth hormone

Sixty crossbred pigs (Large White x Landrace) were used in a 2 x 2 x 2 factorial experiment to investigate the effects of gender (intact males vs females) and strain (A vs B) on the response to exogenous porcine growth hormone (pGH) administration (0 [excipient-treated] vs .1 mg pGH.kg live weight-1.d-1). All pigs had ad libitum access to their diet; pGH was administered daily from 60 to 90 kg live weight. All aspects of growth performance and body composition were affected to different degrees by gender and pGH. Strain A pigs had a higher capacity for protein accretion, superior growth performance and contained less fat in the eviscerated carcass and empty body compared with Strain B pigs. Within each strain, intact males ate more feed, had a higher rate of protein deposition and exhibited faster and leaner growth than females. Exogenous pGH administration increased average protein deposition and growth rate by 84 and 34%, respectively, and reduced average feed intake, fat deposition rate, feed:gain and carcass fat content by 14, 59, 37 and 33%, respectively. The magnitude of the changes in growth performance, tissue accretion rates and body composition elicited by pGH were independent of strain. However, within each strain the improvement in feed:gain and reduction in carcass fat measurements elicited by pGH were proportionately larger for females than for intact males.     

Effects of ruminal infusion of volatile fatty acids on plasma concentration of growth hormone and insulin in sheep.

In an initial experiment we observed postprandial changes in plasma concentrations of growth hormone (GH), insulin, glucagon, and somatostatin (SRIF) in sheep. We then examined whether increasing the rumen concentration of volatile fatty acids (VFA) by infusing a VFA mixture at three rates (53.5, 107, and 214 micromol/kg/min for 4 hr) mimicked the postprandial changes in hormone secretion. Feeding significantly (P < 0.05) suppressed the plasma GH concentration for 6 hr, whereas it significantly (P < 0.05) increased plasma concentrations of insulin, glucagon, and SRIF. Plasma glucose levels tended to decrease after feeding but then gradually increased over the prefeeding level (P < 0.05). Intraruminal infusion of the VFA mixture at 107 micromol/kg/min caused similar changes in ruminal VFA concentrations to those seen after feeding. The infusion significantly (P < 0.05) suppressed GH secretion in a dose-dependent manner, whereas it caused a significant (P < 0.05) increase in insulin and glucose concentrations without changing glucagon concentrations. From these results, we conclude that the postprandial change in ruminal VFA concentration may be a physiological signal which modifies GH and insulin secretion in sheep.     

Effects of obesity on insulin and glucose metabolism in cyclic heifers

Effects of degree of obesity on basal concentrations of insulin, glucose, thyroxine (T4), triiodothyronine (T3), estradiol-17 beta (E) and progesterone (P) were measured in serum from 50 estrous and 73 diestrous Holstein heifers and the insulin response to glucose infusion was assessed in diestrous obese (n = 7) and lean (n = 7) heifers. Basal concentrations of glucose, T4, T3, E and P were not correlated with degree of obesity, although concentrations of glucose, T4 and T3 were higher (P less than .05) at estrus than diestrus. Basal concentrations of insulin at estrus and diestrus were positively correlated (r = .6; P less than .001) with degree of obesity but this relationship was different (P less than .001) between estrus and diestrus. Furthermore, there was interaction (P less than .001) between body condition and stage of the estrous cycle only for basal concentrations (mean +/- SE) of insulin, with the difference in insulin levels (microU/ml) between 12 obese and 12 lean heifers at diestrus (11.7 +/- 1.3 vs 6.7 +/- .6; P less than .05) increasing during estrus (21.9 +/- 2.4 vs 10.8 +/- 1.3; P less than .001). Insulin response to glucose infusion was greater in obese than in lean heifers, whether determined as actual concentration (P less than .01) or as insulin response areas (P less than .05) above base-line concentrations. Obese heifers were less responsive to insulin since hyperinsulinemia and euglycemia coexisted, and because glucose fractional removal rates were similar in both groups after glucose infusion in spite of greater concentrations of insulin in obese heifers. Thus, obesity in heifers was associated with insulin resistance, basal hyperinsulinemia and greater glucose-induced secretion of insulin.     

Effects of growth hormone on tissue metabolism in broiler chicks.

1. The effect of bovine growth hormone (GH) on cartilage, liver, muscle, pancreas and spleen has been investigated. 2. Tissue RNA was elevated in the liver, muscle and spleen of the GH-treated chicks while uptake of radioactive phosphate into RNA was stimulated for both liver and spleen. 3. The GH-treated chicks had an increased cartilage protein content together with a higher rate of incorporation of 14C-methionine pancreatic protein.     

Acute effects of beta-adrenergic agonists on porcine adipocyte metabolism in vitro

Backfat was obtained at slaughter from market weight hogs to study the acute effects of clenbuterol (CB), ractopamine (RAC) or epinephrine (EPI), in the presence and absence of theophylline (THEO) or adenosine deaminase (ADA), on rates of lipolysis and fatty acid synthesis in vitro. Only EPI increased lipolytic rate in the absence of THEO or ADA. In the presence of THEO or ADA, RAC and CB were lipolytic, although CB had a lower maximal response. With THEO present, RAC and EPI increased lipolysis with a similar potency and responsiveness. Lipolytic responses from all agonists were prevented by propranolol. Insulin stimulated glucose incorporation into fatty acids 50 to 100%; stimulated rates were not influenced by any agonist, either alone or in the presence of ADA. When THEO was present, EPI and RAC inhibited fatty acid synthesis approximately 50%. Clenbuterol was not inhibitory under any conditions. Results indicate that, under appropriate conditions, beta-adrenergic agents increase lipolysis and decrease lipogenesis in porcine adipocytes. Combined evidence suggests that lipolysis is more sensitive to beta-adrenergic stimulation than is insulin-stimulated lipogenesis. Finally, RAC and CB possess only partial agonist activity relative to EPI, CB being least active.     

Effect of spray-dried plasma and lipopolysaccharide exposure on weaned pigs: I. Effects on the immune axis of weaned pigs

A study was conducted with 20 weaned barrows (14 d, 4.98 +/- .21 kg) to determine the effect of spray-dried plasma (SDP) on the pig's immune response to a lipopolysaccharide (LPS) challenge. After weaning, pigs were fed a diet containing 0 or 7% SDP for 7 d. On d 6 postweaning, all pigs were fitted with a jugular catheter. On d 7 postweaning, the pigs were given an i.p. injection of either saline or LPS (150 microg/kg BW) followed by a 3-h blood collection every 15 min. Following blood collection, all pigs were killed and tissue was collected for mRNA analysis. Additionally, the small intestine was collected for measurement of villus height, crypt depth, and villus height:crypt depth ratio (VCR) at three sites (25, 50, and 75% of the total length). Feeding SDP resulted in reduced (P < 0.05) mRNA expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA in the adrenal gland, spleen, hypothalamus, pituitary gland, and liver. Additionally, expression of IL-6 mRNA was reduced (P < 0.05) in the spleen and pituitary gland for pigs fed SDP. For pigs fed the diet with SDP, LPS administration did not affect (P > 0.10) cytokine mRNA expression, whereas LPS reduced expression of TNF-alpha mRNA in the spleen and IL-1beta mRNA in the adrenal gland, spleen, and thymus for pigs fed the diet without SDP. For pigs fed the diet with SDP, LPS caused serum TNF-alpha to increase 150-fold compared to a 60-fold increase for pigs fed the diet without SDP. Similarly, interferon-gamma (IFN-gamma) increased 110-fold for pigs fed the diet with SDP compared to a 16-fold increase for pigs fed the diet without SDP. For pigs fed the diet with SDP, LPS caused major villus atrophy, whereas for pigs fed the diet without SDP, LPS had no effect on intestinal morphology. These results demonstrate that the basal activation of the immune system appears to be less for pigs fed the diet with SDP compared to pigs fed the diet without SDP after weaning. Additionally, for pigs fed the diet with SDP, there appeared to be an overresponse of the immune system following LPS administration, which resulted in major damage to the mucosa of the gastrointestinal tract.     

Effects of frequency of recombinant porcine somatotropin administration on growth performance, tissue accretion rates, and hormone and metabolite concentrations in pigs.

Thirty-two crossbred barrows were used to determine the effects of frequency of administration of equivalent total dosages of recombinant porcine somatotropin (rpST) on growth performance, tissue accretion rates, and hormone and metabolite status of pigs. Treatments were control (buffer-injected daily), 60 micrograms/kg BW daily (4 injections/4 d), 120 micrograms/kg BW injected every other day (2 injections/4 d), or 240 micrograms/kg BW given every 4th d (1 injection/4 d). Treatments were initiated at 35 BW and continued until each pig had consumed a total of 440 Mcal of DE intake. Pigs were fed a diet that contained 16% CP, 1.2% lysine, and 3.5 Mcal of DE/kg at 85% of calculated ad libitum intake. Feed intake and rpST dose were adjusted at 8-d intervals. The 240 micrograms/kg BW treatment did not decrease appetite beyond the 15% restriction already imposed in the experimental design. Treatment groups responded to rpST in a frequency-dependent manner. Average daily gain was improved by 10, 23, and 36%, respectively, as injection frequency was increased from 1/4 to 2/4 to 4/4 d. Muscle weights were increased uniformly (15% on average) on a BW basis by all rpST treatments. Carcass (21, 42, and 63%), visceral (43, 65, and 112%), and empty body (22, 43, and 65%) protein accretion rates were increased by rpST treatment in a frequency-dependent fashion, respectively. Lipid accretion also was reduced in carcass and empty body (31% on average) by all rpST injection schemes relative to controls; however, visceral lipid accretion was increased by 59% by rpST. Protein utilization efficiency increased linearly by 24, 45, and 65% as the frequency of injection of rpST was increased from 1/4 to 2/4 to 4/4 d. Hormones and metabolites exhibited frequency-related profiles as well. These results suggest that frequency of administration greatly influences the magnitude of responsiveness to rpST and that optimal benefit would be realized by a delivery system that mimicked a daily surge, at minimum, of rpST.     

Effects of porcine sometotropin on calcium and phosphorus balance and markers of bone metabolism in finishing pigs.

Six sets of four littermate barrows initially averaging 75.5 kg BW were equally fed (within blocks) fortified corn-soybean meal diets (1.30% lysine) containing two concentrations of Ca (.50 and 1.00%) and P (.45% and .90%) in a 34-d test. One-half of the pigs were injected with 4 mg of porcine ST (pST)/d. Following a 7-d adjustment period, total collection of feces and urine was performed during two periods (d 1 to 10 and d 20 to 30) for the determination of Ca and P apparent digestibility (absorption) and retention. Pigs were bled after each period (d 10, 20, and 30) for the determination of serum metabolites associated with Ca, P, and bone metabolism. Feed intake for the 30-d period averaged 2,020 g/d. There were no treatment x period interactions, so the absorption and retention data were pooled across periods. The absorption and retention of Ca and P were greater (P<.01) in pigs fed the higher Ca and P levels. Within each Ca and P level, pST reduced (P<.01) fecal Ca and P excretion. Administration of pST did not affect urinary P excretion, but it increased (P<.03) urinary Ca excretion in pigs fed the low-Ca diet. The absorption and retention of Ca and P were increased (P<.01) by pST; however, the increases in Ca retention and P absorption and retention on an absolute basis (g/d) were more pronounced in pST-treated pigs consuming the higher Ca and P diet (interaction, P<.10). Serum concentrations of 1,25-dihydroxyvitamin D3, osteocalcin, and IGF-I on d 10 and 30 were increased (P<.07) with pST administration. However, the increases in 1,25-dihydroxyvitamin D3 and osteocalcin in pST-treated pigs were more pronounced when the lower dietary Ca and P levels were fed (interaction, P<.08). Urinary excretion of hydroxyproline increased (P<.01) with pST administration, but this effect was more pronounced in pST-treated pigs fed the lower Ca and P diet (interaction, P<.09). These results suggest that pST increases the absorption and retention of Ca and P independent of dietary Ca and P level. However, serum measures associated with Ca, P, and bone metabolism in pST-treated pigs were dependent on the Ca and P content of the diet, suggesting an effect of pST on the homeostatic control of Ca, P, and bone metabolism.     

In vitro effects of insulin on glucose and lipid metabolism in rat embryos

Glucose is utilized for oxidation and synthesis of various lipids in cultured rat embryos. The present experiment examined the effect of insulin on the incorporation of glucose into lipid fractions in rat embryos in vitro . Embryos at the 2-cell, 8-cell and blastocyst stages were incubated for 5 h in hamster embryo culture medium (HECM)-1 containing ¹⁴C-glucose and 170 nmol/L insulin, or in HECM-1 containing only ¹⁴C-glucose, and the oxidation of glucose in these embryos was examined. In addition, the total lipids of blastocysts were separated by thin layer chromatography and the radioactivity of the separated lipid fractions was measured. Oxidation of glucose was significantly increased after insulin treatment compared with that without insulin treatment in 8-cell embryos and blastocysts ( P  < 0.05), but not in 2-cell embryos. Incorporation of glucose into lipids in blastocysts was significantly lowered by insulin treatment compared with that without insulin treatment ( P  < 0.05). Most of the radioactivity was recovered from triacylglycerols of blastocysts and the remaining radioactivity was found in other neutral lipids and phospholipids. We conclude that insulin accelerates the utilization for oxidation of glucose and inhibits the storage of triacylglycerols in rat blastocysts.     

Effects of recombinant porcine somatotropin on growth and carcass traits in meishan pigs

Effects of recombinant porcine somatotropin (rpST) on growth, feed intake, feed conversion, back-fat thickness and lean percentage were examined in growing Meishan pigs. The experiment comprised 42 barrows of which 20 were administered 14 mg rpST twice a week i.m., starting at 40 kg, the others received a placebo. Pigs were fed ad libitum a diet containing 9.2 MJ net energy and 156 g crude protein kg⁻¹ and were slaughtered at 90 kg liveweight. From 40 to 90 kg liveweight, rpST effects were: daily gain +17.9%; feed intake −5.1%; feed conversion −17.5%; backfat thickness −29.8%; lean percentage +16.0%. The effects of rpST in Meishan are much larger than in a similar experiment with leaner western pigs. Development of synthetic breeds with Meishan in combination with the use of rpST in cross-bred fattening pigs may be a way to economically exploit the high fertility of Meishan.     

Serum glucocorticoids, growth hormone and insulin and plasma glucose in bulls given prostaglandin E2 or F2 alpha 1.

Plasma glucose and serum insulin, growth hormone and glucocorticoid concentrations were determined in five yearling bulls given (im) 5, 15 or 30 mg prostaglandin E2 (PGE2), 30 mg prostaglandin F2 alpha(PGF2 alpha) or saline. Jugular blood was collected at frequent intervals around the time of injection and at .5--hr intervals from 1 to 9 hr after injections. Thirty milligrams PGE2 and 30 mg PGF2 alpha each caused 15- to 20-fold increases in serum glucocorticoids. Glucocorticoids increased with increasing doses of PGE2. Although PGE2 and PGF2 alpha each increased blood growth hormone, this effect was about twofold larger after PGE2. By contrast, PGE2 depressed serum insulin about 50% for 1 hr, then insulin increased about sixfold until 3 to 4 hours. Blood serum insulin increased after PGF2 alpha, but this effect only approached significance (P less than .10). Plasma glucose increased about 10 mg/100 ml after PGE2, but was not affected significantly by PGF2 alpha. Thus, the effects of PGE2 and PGF2 alpha on hormones which control glucose metabolism differ markedly. We speculate that PGE2 caused a twofold increase in growth hormone secretion within 10 to 20 min, that increased growth hormone induced increased blood glucose within 1 to 2 hr and that increased glucose caused increased insulin secretion at 2 to 4 hr, but we cannot rule out a transitory (1 hr) suppressive effect of PGE2 directly on the pancreas.     

Acute changes in pancreatic insulin secretion and hepatic glucose kinetics in endotoxemic miniature pigs

We have proposed a misinformed B-cell hypothesis to describe the effects of increased glucose flux across the pancreatic B cell early in endotoxemia, whereby those cells might misinterpret the true glycemic state and thus induce increased insulin release. This hypothesis was supported by the observations that [6-3H]glucose-derived rates of glucose disappearance increased before systemic hyperinsulinemia appeared in endotoxemic Yucatan miniature pigs. Reevaluation of this hypothesis later showed that pancreatic insulin secretion increased before any changes in systemic glucose disappearance or insulin concentrations and, because of significant increases in hepatic insulin extraction, may have led to some local effects of insulin on hepatic carbohydrate metabolism. The present study was conducted with more frequent sampling periods early during endotoxemia to further characterize the effects of this initial acute increase in pancreatic insulin secretion on hepatic glucose uptake, concomitant to net hepatic glucose production, as well as to further clarify the temporal relationships between pancreatic insulin release and the onset of hypoglycemia. We found that an increase in pancreatic insulin secretion is, indeed, the first event to occur, 30 minutes after initiation of endotoxin infusion, coincidental to the onset of significant decreases in portal and hepatic venous blood flow. [3(3)H]Glucose-derived rate of glucose disappearance first increased significantly at 60 minutes, and net hepatic glucose output increased significantly after 80 minutes of endotoxin infusion. Net [3(-3)H]glucose uptake by the liver occurred through 50 minutes of endotoxin infusion. After this, there was a significant reversal in transhepatic isotope kinetics, resulting in net release of [3(-3)H]glucose from the liver for the duration of endotoxin infusion (140 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)