Insulin-like Growth factor-I In Milk Research Articles

Effects of goat milk fractions on the stability of IGF-I in simulated gastrointestinal conditions

The effects of goat milk fractions on the stability of insulin-like growth factor I (IGF-I) digested in the simulated gastrointestinal juice in vitro were investigated. IGF-I concentration was analyzed using an immunological sandwich-type ELISA method. The results showed that the concentration of pure IGF-I in simulated gastrointestinal juice decreased rapidly with the increasing digestion time. However, IGF-I in goat milk was more stable than pure IGF-I either in simulated gastric or intestinal juice. Goat milk and whey and whey supernatant fractions all effectively inhibited the proteolytic degradation of IGF-I in both the simulated gastric and intestinal juices. Dietary derived protease inhibitors, such as soya bean trypsin inhibitor (SBTI), lima bean trypsin inhibitor (LBTI) and egg white protease inhibitor (EWPI) all prevented IGF-I degradation in the simulated gastrointestinal juice, but the whey supernatant fraction represented more effective inhibition than the inhibitors. These results suggested that the whey supernatant fraction might contain specific inhibitors that protect IGF-I from the proteolytic degradation in the simulated gastrointestinal conditions, which was further verified by SDS-PAGE. Therefore, the whey supernatant fraction in goat milk could be a potential resource for the development of the effective oral IGF-I-based products.

Milk production and hormonal changes in Murrah Buffaloes administered recombinant Bovine Somatotropin (rBST)

Investigation was carried out to determine the influence of short term administration of recombinant bovine somatotropin (rBST) on plasma growth hormone (GH), Insulin like growth factor–I (IGF-I), prolactin (PRL) and milk production of buffaloes in early lactation. Experimental buffaloes received i.v. rBST infusion in jugular vein @ 5mg/hr. i.v. for 5 days, while control group was given placebo injection. Blood samples were collected for 5 consecutive days before, during and after treatment and plasma GH, IGF-I and PRL levels were measured. Administration of rBST increased plasma GH (P<0.01) and IGF-I (P<0.01) concentration simulating to increased milk yield (P<0.01). Milk IGF-I concentration was more after cessation of treatment (P<0.05) than before and during the treatment period. The milk yield increased by 29.9% during the experiment (P<0.01) in comparison to control. rBST treatment influenced milk protein (P<0.01) and lactose (P<0.01) without affecting plasma glucose and NEFA, milk NEFA, citric acid and fat content. There was no adverse effect of rBST on mammary health and plasma prolactin concentration. The positive correlation of GH and IGF-I with milk yield indicated a galactopoietic effect of both the hormones to augment milk production in buffaloes.

Vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-I and platelet-derived growth factor levels in human milk of mothers with term and preterm neonates

Human milk is a complex biological fluid. It contains many nutrients, anti-infectious and biologically active substance. Human milk also contains many angiogenic polypeptides. We have determined four of these: Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), insulin-like growth factor- I (IGF-I) and platelet-derived growth factor (PDGF). The aim of this study was to compare the concentrations of VEGF, b-FGF, IGF-I and PDGF in human milk collected from mothers with preterm and term neonates. Human milk samples were collected from 29 mothers of preterm (<37 weeks) and from 29 mothers of term (38 > weeks) infants at days 3, 7 and 28 postpartum. Milk samples were analyzed for VEGF, b-FGF and PDGF by enzyme-linked immunosorbent assay and IGF-I was measured by radioimmunoassay method. Human milk levels of VEGF, IGF-I and b-FGF were significantly higher ( p < 0.001). Furthermore, within-preterm group concentrations of VEGF, IGF-I and PDGF significantly differed during postpartum days 3–7–28 ( p < 0.001, p < 0.05, p < 0.001, respectively), but did not do so for b-FGF concentrations. In term groups, concentrations of IGF-I and VEGF significantly differed ( p < 0.05, p < 0.001, respectively), but did not do so for concentrations of b-FGF and PDGF. This is the first report of simultaneous measurements of four major angiogenic factors in human milk collected from mothers with preterm and term. Our results suggest that three of four angiogenic factors, VEGF, b-FGF and IGF-I, are higher concentration in human milk which collected from preterm mothers than those of terms.

Mammary Specific Transgenic Over-expression of Insulin-like Growth Factor-I (IGF-I) Increases Pig Milk IGF-I and IGF Binding Proteins, with no Effect on Milk Composition or Yield

IGF-I regulates lactation by stimulating mammary mitogenesis, inhibiting apoptosis, and partially mediating the effects of growth hormone on lactogenesis. Herein, lactation performance during first and second parity was assessed in transgenic swine (TG) that over-expressed human IGF-I in milk under the control of the bovine alpha-lactalbumin promoter, regulatory regions and signal peptide coding sequence. Milk samples were collected throughout lactation (farrowing to d24) from TG sows and non-transgenic littermates (CON) and IGF-I, IGF-II, and IGFBP determined. Colostral (<24 h postpartum) IGF-I content was 26-fold greater (p<0.001) in TG sows (949+/- 107 microg/L; range 228-1,600 microg/L) than CON (36+/-17.8 microg/L) and was 50- to 90-fold greater (p< 0.001) in mature milk (d2-24 postpartum). There was no effect of parity on milk IGF-I content. Milk IGF-II concentration was unaffected by IGF-I over-expression. Low molecular weight IGFBP (IGFBP-2 and -5) in the milk of TG sows were higher (p=0.02) than CON in the early postpartum period, but did not differ in mature milk. Milk yield, determined by weigh-suckle-weigh, was similar in TG and CON as was litter weight gain. Milk nutrient composition was not significantly affected by IGF over-expression. Thus, mammary specific transgenic over-expression of IGF-I significantly increased milk IGF-I and IGFBP content, but did not impact lactation performance in swine.

Relationships between the plasma concentrations of insulin-like growth factor-I in dairy cows and their fertility and milk yield

The relationships between insulin-like growth factor-I (IGF-I) and the fertility and milk yield of Holstein-Friesian dairy cows were investigated. The concentration of IGF-I in blood was measured weekly from one...

Insulin-like Growth Factor-I and Piglet Intestinal Development

Abstract Porcine milk contains hormones and growth factors that stimulate piglet intestinal growth and development. Milk-borne insulin-like growth-factor-I (IGF-I) has received considerable attention. In swine, IGF-I concentrations range from 0.10 to 0.4 mg/L in colostrum and approximately 0.01 to 0.04 mg/L in mature milk. Two experimental approaches have been utilized to investigate the role of orally administered IGF-I in neonatal intestinal development. In the first approach, piglets were reared on sow milk replacer formulas containing recombinant human IGF-I (rhIGF-I) at concentrations of 0.1 to 12 mg/L. The advantage of this approach is that specific effects of IGF-I can be assessed in the absence of other bioactive components, changes in milk composition, and other environmental factors. However, the applicability to swine production is limited. A second approach has been to develop transgenic mice or swine that overexpress IGF-I in milk under the direction of promoter regulatory elements of milk proteins to result in animals experiencing mammary specific overexpression of IGF-I during lactation. Herein, the effect of orally administered IGF-I on neonatal intestinal development in artificial rearing studies, as well as studies utilizing transgenic overexpression of IGF-I in milk, was reviewed. Both rhIGF-I in formula or transgenic IGF-I overexpression increased villus growth and disaccharidase activity; however, these effects were primarily observed late in the suckling period (d 21 postpartum) in piglets suckling IGF-I transgenic sows. We speculate that piglets suckling IGF-I transgenic sows may have improved intestinal health during the weaning transition.

Intramammary Infusion of Insulin or Long R3 Insulin-like Growth Factor-I did not Increase Milk Protein Yield in Dairy Cows

Two experiments investigated the regulation of milk protein synthesis in well-fed cows (n = 4) using 1) a hyperinsulinemic-euglycemic clamp and 2) intramammary infusion of insulin or long R3 insulin-like growth factor-I plus supplementary amino acids. In experiment 1, insulin was infused at 1.0µg · kg BW–1 · h–1 to increase circulating levels fourfold, and euglycemia was maintained by infusion of glucose. An insulin clamp increased the yields of casein and whey protein both with and without supplementary amino acids. Plasma concentrations of insulin-like growth factor-I were increased and insulin-like growth factor binding protein-2 decreased during insulin clamp, while both insulin and insulin-like growth factor-I in milk were elevated by this treatment. Milk concentrations of insulin peaked on day 4, but insulin-like growth factor-I concentrations in milk peaked on day 1 of the insulin clamp. In experiment 2, intramammary infusion of insulin had no effects on any measured variables, while yields of milk, protein, and fat were slightly lower following long R3 insulin-like growth factor-I treatment. This could be associated with an increase in somatic cell count, which occurred following long R3 insulin-like growth factor-I treatment. Results from experiment 1 suggest insulin and insulin-like growth factor-I are likely candidates responsible for the increased milk protein yields during the insulin clamp. However, in experiment 2 neither hormone enhanced milk protein yield when administered using an intramammary technique.

Differential Changes in the Milk Concentrations of Epidermal Growth Factor and Insulin-like Growth Factor-I during Lactation in the Tammar Wallaby, Macropus eugenii

Insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) have been measured in milk during lactation of the tammar wallaby ( Macropus eugenii) and related to the total growth-promoting activity of the milk as determined in cultured L6 rat myoblasts. EGF increased throughout lactation from 10ng/ml at 99 days to 25ng/ml at 263 days. As a greater increase occurred with total soluble proteins in the milk, the EGF content per milligram of protein was decreased slightly during lactation. That EGF is secreted in tammar milk at a relatively constant amount is consistent with data from eutherian mammals, even though actual EGF concentrations either decrease during lactation in those species. A very different pattern of secretion was observed with IGF-I, which increased sixfold to a maximum of 1043 ng/ml at 205 days of lactation before falling to approximately 300 ng/ml toward the end of lactation. The protein synthesis-stimulating activity of the milk measured in myoblasts demonstrated a similar pattern to that obtained with IGF-I. The IGF-I changes are unlike the data reported in eutherian mammals in which this growth factor falls to low levels from high concentrations in initial colostrum. The highest concentration of IGF-I in tammar milk coincides with the changeover to a high fat, high protein, low hexose milk composition that is produced at an increased rate when the young leaves the pouch. IGF-I in tammar milk may be important for mammary gland maturation at this stage.

Somatotropin and insulin-like growth factor-I concentrations in plasma and milk after daily or sustained-release exogenous somatotropin administrations

Effects of daily injectable or sustained-release bovine somatotropin (bST) administrations on plasma and milk bST and insulin-like growth factor-I (IGF-I) concentrations were monitored in 74 lactating cows through early, mid- and late lactation. Treatments beginning at wk 4 of lactation were excipient (CO, 24 cows) at 2 wk intervals, daily injections of 10.3 mg bST (DI, 25 cows) and 350 mg sustained-release bST at 2 wk intervals (SR, 25 cows). The duration of treatments was 40 wk. Data were first analyzed for the overall mean concentrations covering the 40 wk treatment period. Overall mean plasma bST, milk bST and plasma IGF-I concentrations were significantly increased by both bST treatments (p<0.05). On the other hand, milk IGF-I concentrations were significantly increased (p<0.05) only in the DI group. Next, data were analyzed according to stage of lactation. The bST treatments resulted in significant increases (p<0.05) in plasma and milk bST concentrations for all early, mid- and late lactation periods. Even though plasma IGF-I concentrations were higher (p<0.05) in all lactation periods for bST treatment groups, higher milk IGF-I concentrations (p<0.05) occurred only in mid- and late lactation periods for the DI group. The patterns of bST and IGF-I concentrations in milk follows those of the plasma after bST treatments.

Mechanism of secretion of plasma insulin-like growth factor-I into milk of lactating goats

125I-Labelled insulin-like growth factor-I (IGF-I) was infused as the free form directly into the pudic artery supplying one gland of lactating goats (n = 6). The infusion was for 60 min and 0.4 +/- 0.09% (S.E.M.) of the infusate was secreted into milk from the infused gland during its first passage through that gland. A large proportion of the 125I-labelled IGF-I escaped into the systematic circulation and was secreted into milk of both glands. A total of 5.2 +/- 0.4% of infused radioactivity was recovered in milk from both glands from 0 to 720 min. Radioactivity consisted of trichloroacetic acid (TCA)-precipitable and -soluble counts which were shown by gel filtration to be authentic IGF-I and degraded products of the peptide. The amount and time course of TCA-soluble radioactivity in milk from both glands was similar, suggesting degradation of 125I-labelled IGF-I at extramammary sites. Maximum specific activity for 125I-labelled IGF-I in milk from the infused gland was reached 80-120 min after the start of infusion and was 2.5-fold greater than milk from the non-infused gland. The time course of appearance of 125I-labelled IGF-I in milk suggests that transfer was via the transcellular pathway and this was further supported by comparing the pattern of transfer of [14C]sucrose and [14C]amino acids. When excess unlabelled IGF-I was included in the infusate, specific activity in milk from the infused gland was reduced to that of the non-infused gland, indicating a competitive and saturable mechanism of secretion for 125I-labelled IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors Affecting Insulin-Like Growth Factor-I Concentration in Bovine Milk

To establish the naturally occurring range of insulin-like growth factor-I concentrations in bovine milk, samples from individual cows (n = 409) managed on five Missouri dairy herds were assayed. Parity, stage of lactation, and farm affected milk insulin-like growth factor-I concentration. Milk insulin-like growth factor-I concentration was higher in early lactation than mid and late lactation with concentrations in multiparous cows exceeding those in primiparous cows. Insulin-like growth factor-I concentration was negatively correlated to milk production the day of sample collection (r = –.15) and not correlated to predicted 305-d milk yields.Unprocessed bulk tank milk samples (n = 100) from a commercial processing plant had a mean concentration of insulin-like growth factor-I in milk of 4.32ng/ml with a range of 1.27 to 8.10ng/ml. This distribution was similar to the range detected in samples from individual cows, but values were lower than those reported for human milk. Concentration of insulin-like growth factor-I in milk was not altered by pasteurization (at 79°C for 45s). However, insulin-like growth factor-I was undetectable in milk heated to temperatures (121°C for 5min) required for infant formula preparation or in commercially available infant formula. These data indicated that insulin-like growth factor-I is a normal but quantitatively variable component of bovine milk that is not destroyed by pasteurization but is undetectable in infant formula. Concentration of insulin-like growth factor-I in bovine milk is lower than concentrations reported for human milk yet similar to those reported for human saliva. Farm, stage of lactation, and parity all have large effects on variability of insulin-like growth factor-I concentration of bovine milk.

The galactopoietic effect of bovine growth hormone in goats is associated with increased concentrations of insulin-like growth factor-I in milk and mammary tissue

Lactating goats exhibiting widely divergent responses to short-term (4 days) treatment with bovine GH (bGH) were retrospectively divided into two groups based on the magnitude of this response. There was no difference between groups in terms of the pretreatment milk yield, but by day 4 of treatment milk secretion had increased by 4.99 +/- 2.5 (S.E.M.) ml/h (P greater than 0.05 compared with pretreatment) for group 1 and 22.9 +/- 2.4 ml/h (P less than 0.001) for group 2. Plasma GH increased in both groups, but concentrations were significantly higher both before and during treatment in group 1 compared with group 2. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly during bGH treatment for both groups and there was no significant difference between the two until day 4 of treatment when levels of IGF-I in group 1 began to decline, whereas those from group 2 were maintained. Concentrations of IGF-I in milk from goats in group 1 were not significantly altered by GH administration, whereas those in goats in group 2 were increased by 40% (P less than 0.01 compared with pretreatment). Levels of IGF-I in mammary secretory tissue from four animals from group 1 were not altered by bGH (2.8 +/- 0.2 and 2.77 +/- 0.08 nmol/kg tissue before and after treatment respectively), but were significantly (P less than 0.05) increased in four animals from group 2 (2.80 +/- 0.2 and 9.9 +/- 1.1 nmol/kg tissue).(ABSTRACT TRUNCATED AT 250 WORDS)

Bovine Growth Hormone: Human Food Safety Evaluation

Scientists in the Food and Drug Administration (FDA), after reviewing the scientific literature and evaluating studies conducted by pharmaceutical companies, have concluded that the use of recombinant bovine growth hormone (rbGH) in dairy cattle presents no increased health risk to consumers. Bovine GH is not biologically active in humans, and oral toxicity studies have demonstrated that rbGH is not orally active in rats, a species responsive to parenterally administered bGH. Recombinant bGH treatment produces an increase in the concentration of insulin-like growth factor-I (IGF-I) in cow's milk. However, oral toxicity studies have shown that bovine IGF-I lacks oral activity in rats. Additionally, the concentration of IGF-I in milk of rbGH-treated cows is within the normal physiological range found in human breast milk, and IGF-I is denatured under conditions used to process cow's milk for infant formula. On the basis of estimates of the amount of protein absorbed intact in humans and the concentration of IGF-I in cow's milk during rbGH treatment, biologically significant levels of intact IGF-I would not be absorbed.

Lactational variation and relationship to postnatal growth of insulin-like growth factor-I in mammary secretions from genetically diverse sows

Mammary secretions obtained from four groups of sows at parturition and on days 7, 14 and 21 of lactation were defatted and assayed for total protein and insulin-like growth factor-I (IGF-I). Sows (n = 57) represented two breeds (Landrace and Duroc) and two genetic lines (selected for differences in sow productivity index, SPI) within each breed. Colostrum of Duroc sows was 4–6 fold and 30–60 fold greater in protein (P < .001) and IGF-I (P < .001) concentrations, respectively, than the corresponding day 7 milk from these sows. In contrast, the colostrum of Landrace sows was 2–3 fold and 30–50 fold greater in protein (P < .001) and IGF-I (P < .001) concentrations, respectively, than the corresponding day 7 milk. The IGF-I content in milk from Duroc sows did not differ among days 7, 14 and 21 of lactation, whereas the IGF-I content of day 7 milk from Landrace sows exceeded those for the corresponding 14 day and 21 day secretion (P < .05). IGF-I concentration in days 14 and 21 milk was higher in Duroc (P < .001 respectively) than Landrace sows. No significant differences in total protein or IGF-I content of mammary secretions were observed between the selected and control lines within each breed. Concentration of IGF-I in colostrum and milk was negatively correlated with: a) SPI (6.5 × number of pigs born alive + adjusted litter weight at day 21 (P < .05)), b) newborn pig survival to day 21 (P < .10) and c) adjusted litter weight at day 21 (P < .05). However, total protein concentration was not associated with any of these parameters. The data demonstrate significant differences in secretory concentrations of IGF-I among pig breeds and may indicate a physiological association between milk IGF-I and growth and survival of neonatal pigs.

Levels of Insulin-Like Growth Factor I in Full- and Preterm Human Milk in Comparison to Levels in Cow’s Milk and in Milk Formulas

The content of insulin-like growth factor I (IGF-I) in human milk, cow's milk and cow's-milk-based infant formulas was determined by radioimmunoassay. The mean levels of IGF-I in full-term milk and preterm milk 0-4 days post partum 2.2 +/- 0.3 and 2.4 +/- 0.5 ng/mg protein, respectively. The IGF-I content in human milk was not affected by gestational age or birth weight and was constantly excreted up to 10 days post partum. The IGF-I content in human milk was significantly higher than that in cow's milk (0.6 +/- 0.1 ng/mg protein, p less than 0.01). IGF-I was not detected in the milk formulas. The IGF-I in human milk might be absorbed or could act locally in the intestine and may be of importance in the nutrition of neonates.

Increased secretion of insulin-like growth factor I into milk of cows treated with recombinantly derived bovine growth hormone.

Six lactating, non-pregnant Jersey cows were given subcutaneous injections of recombinantly derived bovine growth hormone for 7 d. Milk yield was increased by 4.5 kg/d on d 7, compared with the average yield of 10.7 +/- 0.4 kg/d (mean +/- s.e.m.) for the 7 d preceding treatment. Concentrations of insulin-like growth factor I (IGF-I) in the milk increased from 0.44 +/- 0.04 nmol/l (mean +/- s.e.m.) during the 7 d preceding treatment to 1.6 +/- 0.2 nmol/l on d 7 of treatment. Taking the increase in milk yield into account the total increase in the secretion of IGF-I into milk of one udder half was 6-fold. Plasma concentrations of total IGF-I rose from 15.5 +/- 1.3 nmol/l (mean +/- s.e.m.) on the day preceding treatment to 56.9 +/- 3.6 nmol/l (mean +/- s.e.m.) on d 7 of treatment. Mammary plasma flow increased from 1.6 +/- 0.09 to 2.2 +/- 0.06 l/min.udder half over the same time. Estimates of the amount of IGF-I that reached the mammary gland gave values of 24 and 116 nmol/min.udder half before and during treatment respectively. IGF-I in milk of treated cows was associated predominantly with proteins ranging from 40,000 to 150,000 mol.wt, but a significant proportion (19%) of the total IGF-I was present in the free unbound form. IGF-I crosslinking studies revealed the presence in milk of one specifically labelled band at 31,000 mol.wt.

Insulin-like growth factor-I and its association with binding proteins in bovine milk

Immunoreactive insulin-like growth factor-1 (IGF-I in bovine milk was quantified. IGF-I was principally assoication with an approximately 45 kDa binding protein. In addition, a small fraction of IGF-I occurred at a molecular weight approximately the same as that of unbound IGF-I. Available binding sites existed on the approximately 45 kDa binding protein. Bound IGF-I was readily dissociated from binding protein by acid treatment. When IGF-I was estimated in milk obtained from primiparous and multiparous cows, mutiparous cows had a higher concentration (40 nmol/1) [corrected] at parturition than primiparous cows (19.2 nmol/1) [corrected]. By day 2 of lactation, IGF-I concentrations were 30 and 50% of initial estimates for multiparous and primiparous cows respectively. the final IGF-I concentration, on day 56 of lactation, was 4.5 nmol/1 [corrected] for combined parity groups. At parturition in multiparous cows, the mass of IGF-I was estimated at 183 and 157 nmol [corrected] for blood and milk pools respectively. Milk, therefore, represents a substantial pool of IGF-I in the cow. The mechanism of the appearance of IGF-I in bovine milk is unknown.