Feeding different amounts of colostrum or only milk replacer modify receptors of intestinal insulin-like growth factors and insulin in neonatal calves

Colostrum intake influences growth and development of the gastrointestinal tract (GIT) in several species and colostral insulin-like growth factors I and II (IGF-I and IGF-II), and insulin are involved in neonatal intestinal tissue growth. We have studied IGF type 1, IGF type 2, and insulin receptors in the intestine of 8-day-old calves fed different amounts of colostrum or only milk replacer. Calves were fed colostrum of the first six milkings on the first 3 days and then milk replacer (GrC(6)) or colostrum only once and then milk replacer (GrC(1)) or they were fed only milk replacer from the beginning, i.e., no colostrum (GrM). Competitive binding studies and ligand blots confirmed the presence of IGF type 1, IGF type 2, and insulin receptors in mucosal cell membranes of duodenum, jejunum, ileum, and colon. The IGF type 1 receptor number in ileum and total intestine in GrC(6) was greater (P<0.05) than in GrC(1) and in GrM, and IGF type 2 receptor number in total intestine was greater (P<0.05) in GrC(6) than in GrM. Insulin binding was best fitted by a model with two binding sites. High affinity insulin receptor numbers in duodenum, ileum, and total intestine were greater (P<0.05) in GrC(6) than in GrM. The data demonstrate that IGF type 1, IGF type 2, and insulin receptors in intestinal mucosa of neonatal calves are influenced by feeding.     

Abundance of message for insulin-like growth factors-I and -II and for receptors for growth hormone,insulin-like growth factors-I and -II,and insulin in the intestine and liver of pre- and full-term calves

The somatotropic axis and insulin are involved in pre- and postnatal development. In pre- and full-term calves (GrP0 and GrN0; born after 277 and 290 d of pregnancy, respectively) and in preterm calves on d 8 of life after being fed for 7 d (GrP8), we studied whether there are differences in the abundance of messenger RNA (mRNA) of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin among different intestinal sites (duodenum, jejunum, ileum, and colon) and whether there are ontogenetic differences during the perinatal period in intestine and liver. Intestinal site differences (P < 0.05) existed in mRNA levels of IGF-I and IGF-II and receptors for GH, IGF-I, IGF-II, and insulin. Abundance of mRNA of IGF-I and -II and of receptors for IGF-I and GH was highest (P < 0.05) in the colon, abundance of the receptor for IGF-II was comparably high in the colon and ileum, and that of the receptor for insulin was similarly high in colon, ileum, and jejunum. Among GrP0, GrN0, and GrP8 groups, there were differences (P < 0.05) in mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin. Abundance of mRNA of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II and insulin was highest (P < 0.05) in GrP0 calves immediately after birth and was primarily seen in the ileum. In liver, the mRNA levels differed (P < 0.05) among groups for IGF-II and receptors for IGF-I, IGF-II, and insulin, and were highest (P < 0.05) for IGF-II in GrP0, for receptors of IGF-I in GrN0, and were higher (P < 0.05) in GrP0 than GrP8 for receptors of IGF-II. In conclusion, mRNA levels of IGF-I and IGF-II and of receptors for GH, IGF-I, IGF-II, and insulin were different at different intestinal sites and in intestine and liver and changed during the perinatal period.     

Effects of peroral insulin and glucose on circulating insulin-like growth factor-I, its binding proteins and thyroid hormones in neonatal calves

There is disagreement in the literature about the ability of neonatal calves to absorb perorally administered insulin. This study evaluated the absorption of a bolus of insulin administered alone or with an energy souce and its effects on the circulating insulin-like growth factor system and thyroid hormones in newborn Holstein-Friesian calves. Within 1 h of dosing, mean serum insulin and triiodothyronine (T3) concentrations had increased considerably, whether the insulin was applied alone (n = 4) or together with glucose (n = 4), accompanied by marked hypoglycemia. No significant changes were observed in control calves (n = 4) given the vehicle solution. Increased serum glucose and T3 concentrations with no change in insulinemia occurred in a 4th group of calves given glucose alone. At 32 h of age and after 3 meals of colostrum there were no differences in glycemia, insulinemia, or proteinemia among the 4 groups of calves examined. Mean serum insulin-like growth factor-I (IGF-I) tended to decrease over this period in the control group. The decrease was more pronounced in the insulin-treated group but absent in both groups that received glucose. These differences were associated with equivalent differences in abundance of the 40-45K IGF-binding protein-3 (IGFBP-3); however, lower molecular mass IGFBPs were not affected. The results show that a pharmacological peroral dose of insulin can lead to rapid systemic alterations in the IGF/IGFBP system in neonatal calves that can be modified by simultaneous administration of a small energy supply in the form of glucose.     

Effect of feed restriction on serum somatotropin, insulin-like growth factor-I-(IGF-I) and IGF binding proteins in cyclic heifers actively immunized against growth hormone releasing factor

Feed restriction often increases serum somatotropin (ST) and decreases insulin-like growth factor-I (IGF-I) in ruminants; however, the mechanisms responsible for this change in ST and IGF-I are not well defined. We investigated the effects of feed restriction on serum ST, IGF-I, IGF binding proteins (IGFBP), insulin and nonesterified fatty acids (NEFA) in cyclic Angus and Charolais heifers (n=15) previously immunized against growth hormone releasing factor (GRFi) or human serum albumin (HSAi). Cows were fed a concentrate diet ad libitum (AL) or were restricted to 2 kg cotton seed hulls (R) for 4 d. Each heifer received each dietary treatment in a single reversal design. As anticipated, GRFi decreased ST, IGF-I and insulin (P<.05). In addition, GRFi decreased serum IGFBP-3 (P<.01), but increased IGFBP-2 (P<.01). Feed restriction resulted in an increase in serum ST in HSAi, but not in GRFi heifers. Regardless of immunization treatment, feed restriction decreased serum IGF-I and insulin, and increased NEFA (P<.01). In conclusion, the increase in serum ST levels observed during feed restriction was blocked by active immunization against GRF. However, feed restriction resulted in decreased serum IGF-I in GRFi heifers in spite of initial low levels of IGF-I (due to GRFi). Although GRFi decreased levels of IGFBP-3 and increased levels of IGFBP-2, feed restriction for 4 d did not alter serum IGFBP.     

Influence of feeding different amounts of first colostrum on metabolic, endocrine, and health status and on growth performance in neonatal calves

Colostrum intake is important for health and postnatal development of neonatal calves. We studied the effects of enhanced first colostrum feeding on growth, health status, and metabolic and endocrine traits in calves during their 1st wk of life. Calves of group CL (GrCL; n = 7) were fed colostrum of milkings 1 to 6 twice daily during the first 3 d of life, followed by milk replacer (MR) up to d 7. Calves of group CH (GrCH; n = 7) were fed colostrum of the first milking during the first 3 d and then colostrum (of the first milking) twice daily, which on d 4, 5, 6, and 7 was diluted with 25, 50, 75, and 75 parts of MR, respectively. Pre- and postprandial blood samples were taken on d 1, 2, 3, and 7 for the determination of various metabolic and endocrine traits, and on d 5 intestinal absorption capacity was measured using the xylose absorption test. Rectal temperatures and fecal scores were higher (P < .05) in GrCH than in GrCL. Plasma concentrations of total protein and albumin were higher (P < .05) on d 7, IgG on d 2 and 3, and urea on d 2, 3, and 7 in GrCH than in GrCL. Plasma concentrations of triglycerides were higher (P < .05) on d 2 and of phospholipids and cholesterol were higher (P < .01) on d 7 in GrCH than in GrCL. Plasma insulin and glucagon concentrations were higher (P < .05) in GrCH than in GrCL, whereas prolactin and growth hormone concentrations were higher (P < .05) in GrCL than in GrCH. Enhanced colostrum intake had no effects on xylose absorption on d 5. Higher plasma protein, urea, and lipid concentrations in GrCH partly mirrored higher protein and fat intake but additionally pointed to higher protein synthesis and lipid turnover.     

Effect in sheep of dietary concentrate content on secretion of growth hormone, insulin and insulin-like growth factor-I after feeding

This study was designed to examine the effects of the proportion of concentrate in the diet on the secretion of growth hormone (GH), insulin and insulin‐like growth factor‐I (IGF‐I) secretion and the GH‐releasing hormone (GHRH)‐induced GH response in adult sheep fed once daily. Dietary treatments were roughage and concentrate at ratios of 100:0 (0% concentrate diet), 60:40 (40% concentrate diet), and 20:80 (80% concentrate diet) on a dry matter basis. Mean plasma concentrations of GH before daily feeding (10.00–14.00 hours) were 11.4 ± 0.4, 10.1 ± 0.5 and 7.5 ± 0.3 ng/mL on the 0, 40 and 80% concentrate diet treatments, respectively. A significant decrease in plasma GH concentration was observed after daily feeding of any of the dietary treatments and these decreased levels were maintained for 8 h (0%), 12 h (40%) and 12 h (80%), respectively (P < 0.05). Plasma IGF‐I concentrations were significantly decreased 8–12 h and 4–16 h after the end of feeding compared with the prefeeding level in the 40 and 80% concentrate diet treatments, respectively (P < 0.05). GHRH injection brought an abrupt increase in the plasma GH concentrations, reaching a peak 10 min after each injection, but, after the meal, the peak plasma GH values for animals fed 40% (P < 0.05) and 80% (P < 0.01) concentrate diet were lower than that for roughage fed animals. The concentrate content of a diet affects the anterior pituitary function of sheep resulting in reduced baseline concentrations of GH and prolonged GH reduction after feeding once daily.     

Interaction of insulin-like growth factors (IGF) with isolated sheep hepatocytes. II. Binding, internalization and degradation of IGF-II

This study examines the binding and degradation of IGF-II by the ovine liver. Binding and degradation of 125I-IGF-II to isolated hepatocytes was time, temperature and cell number dependent. Ovine and human IGF-II were 2-5 times more effective in inhibiting 125I-hIGF-II binding than were the IGF-I preparations. Insulin did not affect binding. Autoradiographs of 125I-hIGF-II affinity cross-linked to hepatocytes showed a major band of molecular weight 271,000 under reduced conditions. This band was eliminated by 100 nM hIGF-II or oIGF-II but not by excess hIGF-I, oIGF-I or insulin. The internalization of IGF-II was examined by treating the cells with trypsin or sodium acetate to remove surface-bound IGF-II. Both treatments showed that 20-25% of 125I-hIGF-II was internalized. Mannose-6-phosphate at 1, 2 and 4 mM enhanced the binding of 125I-hIGF-II to hepatocytes 3.5, 12.8 and 16.4%, respectively. The lysosomal inhibitors ammonium chloride, chloroquine and leupeptin had no effect on 125I-hIGF-II degradation or cell-associated radioactivity indicating a nonlysosomal pathway of degradation for 125I-hIGF-II in the ovine hepatocyte. The low molecular weight sheep serum IGF binding protein inhibited binding of 125I-hIGF-II in a dose-dependent manner but had no effect on degradation, which suggests that degradation of 125I-hIGF-II is independent of receptor interaction. These studies demonstrate that IGF-II binds to specific high affinity sites in sheep hepatocytes which display the characteristics of type II IGF receptors. A significant fraction of the receptor bound IGF-II is internalized but not degraded by these cells, which suggests that the biological actions of IGF-II may be exerted by an intracellular pathway in sheep hepatocytes.     

Insulin-like growth factor (IGF)-I and IGF binding proteins-2, -3, -4, -5 in porcine corpora lutea during the estrous cycle; evidence for inhibitory actions of IGFBP-3

In this study we measured protein concentrations of insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) 2-5 in porcine corpora lutea (CLs) throughout the estrous cycle (Experiment 1), and examined the effects of IGFBP-3 and IGFBP-3 antibody (AB) on luteal progesterone (P4) secretion in vitro (Experiment 2). For Experiment 1, (CLs) and serum were collected on days (D) 4, 7, 10, 13, 15 and 16 of the estrous cycle (n = 5 animals per day). IGF-I was extracted from CLs and sera, and measured by radioimmunoassay (RIA). IGFBPs were measured in CLs by ligand blots. For Experiment 2, CLs (from Experiment 1) were enzyme dissociated and luteal cells cultured (24 h) in Medium 199 (M199) containing (0-500 ng/ml) IGFBP-3 (+/-IGF-I; 100 ng/ml), or (0-10 microg/ml) IGFBP-3 AB. P4 in media was measured by RIA. In Experiment 1, luteal IGF-I concentrations (ng/g tissue) were maximal on day 4 and gradually decreased thereafter. Serum IGF-I concentrations (ng/ml) were highest on days 4 and 7, compared with days 10-15. Peak levels of luteal IGFBP-3 were also seen on days 4 and 7 of the cycle. Luteal IGFBP-2 concentrations showed a tendency to increase on day 16 (P < 0.05 versus day 10), but no significant changes in IGFBP-4 or -5 were seen. In Experiment 2, IGFBP-3 (w IGF) inhibited the steroidogenic actions of IGF-I, but had no significant actions alone (IGFBP-3 w/o IGF). Finally, IGFBP-3 AB stimulated P4 secretion on days 4 and 7, but not on days 10-16. We conclude that IGFBP-3 inhibits IGF-I actions in the porcine CL.     

Effects of acute thermal stress and amount of feed intake on concentrations of somatotropin, insulin-like growth factor (IGF)-I and IGF-II, and thyroid hormones in plasma of lactating Holstein cows

Our objective was to evaluate effects of acute thermal stress, independent of reduced feed intake caused by elevated temperatures, and of reduced feed intake in thermal comfort on plasma concentrations of somatotropin, insulin-like growth factors I and II, thyroxine, and triiodothyronine. Six Holstein cows (averaging 475 +/- 18 kg BW, 2.3 +/- .3 parities, and 96 +/- 12 d in lactation) surgically fitted with catheters in the hepatic portal vein, mesenteric vein, and intercostalis posterior artery were exposed to treatments of thermal comfort environments with ad libitum or restricted (75% of ad libitum) DM intake and a thermal stress environment with ad libitum intake in two balanced 3 x 3 Latin squares. Thermal stress increased rectal temperatures and respiration rates. Dry matter intake of the thermal-stressed cows offered feed ad libitum (11.1 +/- .7 kg/d) was similar to the experimentally imposed reduction in DM intake of the thermal comfort restricted group (11.5 +/- .7 kg/d). Dry matter intake of cows in thermal comfort was 15.1 +/- .7 kg/d. Plasma somatotropin concentrations tended (P less than .08) to decrease during thermal stress but were unchanged by amount of feed intake in thermal comfort environments. Concentrations of IGF-I were not affected by treatments. Concentrations of IGF-II tended (P less than .14) to increase with thermal stress compared with thermal comfort treatments. Thyroxine concentrations tended (P less than .15) to increase in the thermal stress treatment compared with the thermal comfort restricted intake treatment. Triiodothyronine tended (P less than .11) to decrease with restriction in feed intake in the thermal comfort environment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of fat supplementation on leptin, insulin-like growth factor I, growth hormone, and insulin in cattle

We investigated the effect of fat supplementation on plasma levels of hormones related to metabolism, with special attention to leptin, in cows in early lactation and in feedlot steers. In experiment 1, 34 lactating cows received no fat or else 0.5 or 1.0 kg of partially hydrogenated oil per day in addition to their basal diet from day 20 before the expected calving date to day 70 postpartum. In experiment 2, part of the corn in the basal concentrate was replaced with 0.7 kg of the same oil such that the diets were isocaloric; 18 cows received the fat-substituted diet and 18 a control diet from day 20 before the expected calving date to day 75 postpartum. In experiment 3, calcium salts of fatty acids were added to the basal diet of 14 feedlot steers for 80 d; another 14 steers received a control diet. The basal plasma levels of leptin were higher in the cows than in the steers. Dietary fat supplementation did not affect the leptin levels in the lactating cows but lowered the levels in the feedlot steers despite greater energy intake and body fatness (body weight) in the steers receiving the supplement than in those receiving the control diet. The levels of insulin-like growth factor I and insulin were decreased with dietary fat supplementation in the lactating cows but were unaffected in the steers, suggesting that responses to fat ingestion depend on the physiological state of the animal, including age and sex. Finally, no effects of supplementary fat on the level of growth hormone were demonstrated in any of the models.     

Influence of topical dexamethasone applications on insulin, glucose, thyroid hormone and cortisol levels in dogs

The influence of two topical dexamethasone applications (dermal and ototopical) on plasma insulin, glucose, thyroid hormone and cortisol levels was investigated in beagle dogs. Both treatments significantly decreased basal cortisol values, associated with exaggerated rise in insulin (∼50%), together with unchanged serum glucose levels. Dermal dexamethasone quickly decreased plasma thyroxin (T₄) levels; whereas dexamethasone in ear drops gradually inhibited time-dependently T₄ release (18–50%). Both formulations blunted plasma triiodothyronine (T₃) levels but the response induced by dermal dexamethasone was stronger than by dexamethasone ear drops. Upon drug withdrawal, insulin secretion returned to baseline a week after treatment cessation, while cortisol, T₄ and T₃ levels did not reach baseline values. These results suggest that topical glucocorticoids unexpectedly trigger secondary hypothyroidism with concomitant suppression of hypothalamic–pituitary–adrenal axis but sensitize the endocrine pancreas, thus, their application needs careful evaluation for surprisingly different effects on endocrine stress axis activity.     

Effects of growth hormone and feeding level on endocrine measurements,hormone receptors,muscle growth and performance of prepubertal heifers

Prepubertal Friesian heifer calves (n = 24, initial BW = 195 +/- 5 kg) were assigned to a 2 x 2 factorial block design and used to evaluate the effects of daily GH treatment (0 or 15 mg/d) at either a low or a high feeding level in a 5-wk treatment period on endocrine measurements, hormone receptors, muscle growth, and overall performance. In the pretreatment period, a low feeding level was employed for all calves. During the treatment period, animals at the low feeding level had free access to a roughage-based mixture, whereas animals at the high feeding level had free access to a concentrate mixture and were offered 2 kg/d of the roughage-based mixture. Blood samples were collected weekly starting 3 wk before treatment. Longissimus (LM) and supraspinatus (SS) muscles were obtained at slaughter. Metabolizable energy intake was 81% higher, digestible CP intake was 140% higher, and ADG was 115% higher (all P < 0.001) at the high vs. low feeding level. Feed (DMI, ME, and protein) intake was not affected by GH treatment, but ADG was 18% higher (P < 0.13) in GH-treated than in control heifers at both feeding levels. Although of different magnitudes, the muscle anabolic effects of GH treatment and high vs. low feeding level were additive, and both treatments increased carcass weights (P < 0.02 and P < 0.001, respectively), LM (P < 0.05 and P < 0.001), and SS (P < 0.06 and P < 0.003). The anabolic effect of GH treatment was similar in both muscles, whereas the effect of feeding level was most pronounced in LM. Overall, GH treatment increased plasma GH, IGF-I (both P < 0.001), and IGFBP-3 (P < 0.02); however, GH treatment increased total IGF-I, free IGF-I, and IGFBP-3, and decreased IGFBP-2 mainly at the high feeding level (GH x feeding level interaction; P < 0.02, 0.01, 0.03, and 0.10, respectively). The high feeding level increased insulin, free and total IGF-I, and IGFBP-3 (all P < 0.001), but decreased GH and IGFBP-2 (both P < 0.001). High feeding increased type-1 IGF receptor density (P < 0.02), mainly in LM, in accordance with the largest anabolic response in this muscle, whereas GH treatment had no effect on type-1 IGF receptors. The results suggest that in skeletal muscle, the anabolic effects of exogenous GH are related to endocrine changes in the GH-IGF axis, whereas the effects of feeding level also seem to rely on IGF receptor density in the muscles.     

Plasma levels of growth hormone, insulin, sugar and acetoacetate in cattle. Diurnal variations and responses to feeding

The fundamental differences between monogastric animals and ruminants as regards the handling of dietary carbohydrates and as regards the relative importance of gluconeogenesis, rise interesting questions as to the factors regulating the secretion of growth hormone and insulin in poly gastric animals.     

Effects of restricted feeding, low-energy diet, and implantation of trenbolone acetate plus estradiol on growth, carcass traits, and circulating concentrations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in finishing barrows

Effects of restricted feeding (80% ad libitum), feeding a low-energy diet containing 84% DE (2.95 Mcal/kg) of the control diet, and implantation of Revalor H (140 mg trenbolone acetate plus 14 mg estradiol-17beta) on growth, carcass traits, and serum concentrations of insulin-like growth factor (IGF)-I and IGFbinding protein-3 (IGFBP-3) were studied in crossbred finishing barrows beginning from 59 +/- 0.9 kg of body weight. Blood samples were taken every 3 wk and the animals were slaughtered at approximately 105 kg body weight. Restricted feeding caused a decrease (P < 0.01) in ADG; feeding the low-energy diet was effective in reducing backfat thickness but decreased gain:feed; the implantation caused a decrease in ADG, feed intake, and backfat thickness and increased gain:feed. Overall pork quality based on pH, drip loss, and the lightness in color of longissimus muscle was not affected by any of the treatments. Serum IGF-I concentration increased following the implantation but did not change (P > 0.05) due to other treatments. Immunoreactive IGFBP-3 concentration was not changed by any of the treatments. Overall ADG was positively correlated with early-stage (d 21) IGF-I and IGFBP-3 concentrations only in unimplanted barrows, whereas backfat thickness was negatively correlated with d-42 IGF-I concentration in all but unimplanted barrows with ad libitum intake. A strong positive correlation (P < 0.01) between IGF-I and IGFBP-3 concentrations was apparent with increasing age of the animals. Results suggest that growth rate and backfat thickness are decreased by a moderate restriction of feed or energy intake with no accompanying changes in circulating IGF-I and IGFBP-3 concentrations and that the beneficial effect of Revalor H implantation on feed efficiency may be mediated, in part, by IGF-I. Moreover, both IGF-I and IGFBP-3 concentrations may be useful as growth indices in pigs.