Plasma Concentrations Of Insulin-like Growth Factor Research Articles

Regulation of Aging Processes: A Perspective of Dietary Restriction Models

The moderate restriction of dietary energy intake (dietary restriction: DR) extends the lifespan and health span of various laboratory animals, suggesting that it delays the aging process inherent in many animal species. Attenuated growth hormone and insulin-like growth factor-1 (IGF-1) signaling caused by mutations also increases the lifespan of mice, even those allowed to feed freely. In nematodes, the Daf16, mammalian Forkhead box O (FoxO) transcription factor, was shown to be required for lifespan extension in response to reduced IGF-1 signaling. Because DR also decreases the plasma concentration of IGF-1 in mammals, the IGF-1-FoxO axis may play a central role in the lifespan extension effect of DR and, thus, retardation of aging. Studies using knockout mice under DR conditions revealed the importance of FoxO1 and nuclear factor erythroid-derived 2-like 2 (Nrf2) in tumor suppression, and FoxO3 in lifespan extension. Human genomic studies also identified a strong association between a FOXO3 single nucleotide polymorphism and longevity. The aging mechanism is the most important risk factor for disease and frailty in aging humans. Therefore, further research on the application of DR to humans, the development of compounds and drugs that mimic the effects of DR, and mechanisms underlying FOXO3 polymorphisms for longevity is highly relevant to extending the human health span.

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = -0.49), systolic blood pressure (SBP) (-0.44), and carotid intima-media thickness (cIMT) (-0.43). The IGF-1R expression was negatively correlated with PWV (r = -0.42) and SBP (r = -0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

Insulin-like growth factor 1 and its prognostic value in the course of acute ischemic cerebrovascular events.

The aim of the study was to evaluate insulin-like growth factor 1 (IGF-1) as a predictor of the course of an acute cerebral ischemic event (AICE). This polypeptide, by activating receptors that are present in most tissues, including the brain, mediates the anabolic activity of growth hormone (GH) and its impact on growth and maturation processes, as well as organisms' survival time. AICE can occur in the form of a transient ischemic attack (TIA) or an ischemic stroke (IS). The study included 86 participants. The correlation between serum IGF-1 concentration and the clinical status of 56 patients on days 1 and 9 of AICE, as well as risk factors and the course of the disease, were prospectively analyzed. The control group consisted of 30 healthy volunteers. Patients with a minor baseline neurological syndrome had higher serum IGF-1 concentrations than patients with severe baseline neurological dysfunctions. Multidimensional analyses showed that high IGF-1 values independently determined the worse course of the disease, especially in patients with a severe neurological deficit present on the first day of AICE. Our results indicate that the high level of circulating IGF-1 on the first day of AICE is an independent factor determining the unfavorable course of the stroke, and this relationship is proportional to the severity of the baseline neurological deficit. The study also revealed a positive correlation between the decreased plasma IGF-1 concentration on the first day of AICE and the severity of neurological symptoms.

Expressions of Insulin-like Growth Factor System among Different Breeds Impact Piglets' Growth during Weaning.

The present study investigated the insulin-like growth factors (IGFs) and their receptors and binding proteins among three pig breeds during weaning. Sixty Duroc (DR), Taoyuan black (TYB), and Xiangcun black (XCB) piglets (20 piglets per breed) were selected at 21 and 24 (3 days of post-weaning) days of age to analyze organ indices, plasma concentrations of IGF and IGF-binding proteins (IGFBPs) using ELISA kits, and gene expression of IGF-system-related components in different tissues. The plasma IGFBP-3 concentration in TYB piglets was higher (p > 0.05) than in the XCB and DR piglets at 21 days of age. At 21 days of age, compared with the DR piglets, the IGF-1 expression was lower (p < 0.05) in the kidney, but it was higher (p < 0.05) in the spleen of XCB and TYB piglets. At 24 days of age, the IGF-1 expression was higher (p < 0.05) in the kidney of TYB piglets than in the XCB and DR piglets, while IGFBP-3 in the stomach and IGFBP-4 in the liver of XCB and TYB piglets were lower (p < 0.05) compared with the DR piglets. Weaning down-regulated (p < 0.05) IGF-1 expression in the jejunum, spleen, and liver of piglets, while it up-regulated (p < 0.05) IGFBP-3 expression in the stomach, IGFBP-4 in the liver, IGFBP-5 in the ileum, and IGFBP-6 in the jejunum of DR piglets. Spearman's correlation analysis showed a negative correlation (p < 0.05) between plasma IGFBP-2 and IGFBP-5 concentration and the organ indices of piglets. Collectively, there were significant differences in the IGF system components among the three pig breeds. The IGF system components were altered during weaning, which might be involved in weaning stress to decrease the growth of piglets.

134-OR: Associations of Growth Hormone (GH) Mediators with Loss of Glycemic Control in Youth with Type 2 Diabetes (T2D)

T2D in youth has a more severe phenotype than in adults, with puberty as a potential contributor to this difference. Pubertal changes in GH mediators (e.g., insulin-like growth factor 1 (IGF-1), growth hormone receptor (GHR), insulin-like growth factor binding protein 1 (IGFBP-1)) may impact insulin sensitivity and beta cell function. We examined associations of GH mediators with loss of glycemic control in youth with T2D using the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort (N= 310). We performed paired comparison of plasma concentrations of IGF-1, GHR, and IGFBP-1 (ELISA), between 0mo and 36mo based on TODAY primary outcome of loss of glycemic control vs. maintained glycemic control (LGC vs MGC), with LGC defined as HbA1c ≥ 8% for 6 months and/or insulin dependence. We studied associations of GH mediators with HbA1c, insulinogenic index, oral disposition index, and 1/fasting insulin. Models were adjusted for age, sex, race, treatment arm, and baseline HbA1c (linear regression). Mean plasma IGF-1 (ng/mL) was lower in LGC group at 0mo (LGC: 451 ± 141, MGC: 485 ± 155, p = 0.04), and at 36mo (LGC: 340 ± 117, MGC: 400 ± 136, p&amp;lt; 0.0001). Increase in IGF-1 between 0-36mo predicted lower HbA1c at 36mo (B = -3.2E-3, SE = 9.0E-4, p &amp;lt; 0.001). Higher GHR was associated with higher HbA1c (B = 1.2E-2, SE = 3.0E-3, p &amp;lt; 0.001) and lower 1/fasting insulin (B = -6.6E-4, SE = 2.1E-4, P &amp;lt; 0.01) at 0mo. Increase in GHR between 0-36mo predicted higher 36mo HbA1c (B = 3.0E-2, SE = 9.4E-3, p &amp;lt; 0.01). IGFBP-1 was positively associated with 1/fasting insulin at 0m (B = 1.1E-3, SE = 4.9E-4, p = 0.03). In exploratory analyses stratified by Tanner stage (TS) at study entry, GH mediators changed differentially between TS 1-3 (n = 31) vs TS 4-5 (n = 274). In conclusion, GH mediators differed based on primary outcome in TODAY, and were associated with HbA1c and insulin sensitivity. Whether changes in GH mediators contribute to, or are the result of, changes in glucose metabolism is a key area for future studies. Disclosure C.Lu: None. D.Wolfs: None. L.El ghormli: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. M.Patti: Consultant; MBX Biosciences, AstraZeneca, Hanmi Pharm. Co., Ltd., Other Relationship; Fractyl Health, Inc. E.M.Isganaitis: None. Funding National Institutes of Health (2T32DK007260-46); National Institute of Diabetes and Digestive and Kidney Diseases (5U01DK061230-16)

Removing maternal heat stress abatement during gestation modulated postnatal physiology and improved performance of Bos indicus-influenced beef offspring.

This study evaluated the growth and immune response of beef calves born from Bos indicus-influenced beef heifers provided pre- and postpartum heat abatement on pasture. On 83 ± 4 d prepartum (day 0), 64 Brangus crossbred beef heifers (~¼ B. indicus) were stratified by body weight (BW; 454 ± 37 kg) and body condition score (BCS; 6.3 ± 0.28; scale 1 to 9), and then allocated into 1 of 16 bahiagrass pastures (1 ha and 4 heifers per pasture). Treatments were randomly assigned to pastures (8 pastures per treatment) and consisted of heifers provided (SH) or not (NSH) access to artificial shade (4.5 m2 of shade area per heifer) from 83 d prepartum to 50 d postpartum (days 0 to 133). Heifers and calves were managed similarly from day 133 until the start of the breeding season (day 203). Calves were weaned on day 203 (at 119 ± 19 d of age), limit-fed the same drylot diet at 3.5% of BW (DM basis) days 209 to 268 (3 to 4 calves per pen; 8 pens per treatment) and vaccinated against respiratory disease pathogens on days 222 and 236. Heifer intravaginal temperatures from days 35 to 42 were lower (P ≤ 0.03) for NSH vs. SH heifers from 0000 to 0800 hours but greater (P ≤ 0.05) for NSH vs. SH heifers from 1100 to 1800 hours. Heifer intravaginal temperature from days 126 to 132 did not differ (P = 0.99) between NSH and SH heifers. Heifers assigned to NSH had greater respiration rates from days 20 to 96 (P ≤ 0.0007), greater plasma concentration of cortisol on days 35 (P = 0.07) and 55 (P = 0.02), less plasma concentration of insulin-like growth factor 1 (IGF-1) on days 35 (P = 0.10), 55, and 133 (P ≤ 0.05), and less BCS from days 55 to 203 (P ≤ 0.01) compared to SH heifers. Calves born from NSH heifers had less birth BW (P = 0.05), greater overall plasma haptoglobin concentrations (P = 0.05), greater seroconversion against bovine respiratory syncytial virus on day 222 (P = 0.02), tended to have greater ADG from days 209 to 268 (P = 0.07), and had greater BW on day 268 (P = 0.05) compared to SH offspring. Plasma concentrations of cortisol and serum titers against other respiratory disease pathogens did not differ (P ≥ 0.15) between NSH and SH offspring. Hence, removing maternal access to artificial shade: (1) increased prepartum intravaginal temperature and plasma concentrations of cortisol but reduced prepartum BCS and plasma concentrations of IGF-1 in grazing B. indicus-influenced beef heifers; and (2) increased post-weaning BW gain and had positive effects on humoral immune response of their offspring.

Effect of voluntary waiting period on metabolism of dairy cows during different phases of the lactation.

An extended calving interval (CInt) by extending the voluntary waiting period (VWP) could be associated with altered metabolism in dairy cows. The aim of this study was first to evaluate the effects of VWP on metabolism and body condition during the first 305 d after the first calving in the experiment (calving 1), around the end of the VWP, and during pregnancy (280 d before calving 2). Second, the effects of the VWP on metabolism were determined from 2 wk before until 6 wk after calving 2. Third, individual cow characteristics were used to predict milk production and body condition of cows after different VWP. Holstein-Friesian cows (N = 154, 41 primiparous [PP], 113 multiparous [MP]) were blocked for parity, milk production, and lactation persistency, randomly assigned to a VWP of 50, 125, or 200 d (VWP50, VWP125, or VWP200) and followed from calving 1 until 6 wk after calving 2. In the first 6 wk after calving 1 and from 2 wk before until 6 wk after calving 2, weekly plasma samples were analyzed for nonesterified fatty acids (NEFA), β-hydroxybutyrate, glucose, insulin, and insulin-like growth factor 1 (IGF-1). From wk 7 after calving 1 until 2 wk before calving 2, insulin and IGF-1 were analyzed every 2 wk. Fat- and protein-corrected milk (FPCM) and body weight (BW) gain were measured weekly. Cows were divided in two parity classes based on calving 1 (PP and MP) and remained in these classes after calving 2. During pregnancy, MP cows in VWP200 had greater plasma insulin and IGF-1 concentration and lower FPCM compared with MP cows in VWP125 (insulin: 18.5 vs. 13.9 µU/mL, CI 13.0-19.7, P < 0.01; IGF-1: 198.5 vs. 175.3 ng/mL ± 5.3, P = 0.04; FPCM: 22.6 vs. 30.0 kg/d ± 0.8, P < 0.01) or VWP50 (insulin: 15.8 µU/mL, P < 0.01; IGF-1: 178.2 ng/mL, P < 0.01; FPCM: 26.6 kg/d, P < 0.01) and had a greater daily BW gain compared with cows in VWP50 (3.6 vs. 2.5 kg/d ± 0.2; P < 0.01). After calving 2, MP cows in VWP200 had greater plasma NEFA concentration (0.41 mmol/liter) compared with MP cows in VWP125 (0.30 mmol/liter, P = 0.04) or VWP50 (0.26 mmol/liter, P < 0.01). For PP cows, the VWP did not affect FPCM or body condition during the first lactation in the experiment, or metabolism after calving 2. Independent of the VWP, higher milk production and lower body condition before insemination were associated with higher milk production and lower body condition at the end of the lactation. Variation in these characteristics among cows could call for an individual approach for an extended VWP.

Spotlight in Plastic Surgery: January 2023.

Spotlight in Plastic Surgery: January 2023.

Effect of dioscorea opposite waste on growth performance, blood parameters, rumen fermentation and rumen bacterial community in weaned lambs

This study investigated the effects of dioscorea opposite waste (DOW) on the growth performance, blood parameters, rumen fermentation and rumen microbiota of weaned lambs. Sixty healthy weaned Small-Tailed Han lambs (male, (22.68±2.56) kg initially) were used as the experimental animals. Four levels of concentrate: 0 (control, CON), 10% (DOW1), 15% (DOW2) and 20% (DOW3), were replaced with DOW in the basal diet as experimental treatments. The results showed that lambs fed the DOW2 diet had a higher (P<0.05) dry matter intake (DMI) than the other groups. There was no significant difference (P>0.05) among DOW groups in average daily weight gain (ADG), and replacing concentrate with DOW linearly or quadratically increased (P<0.05) the ADG, while lambs fed the DOW2 diet showed greater (P<0.05) ADG than the CON group. The relative plasma concentration of growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin were affected by DOW, replacing concentrate with DOW linearly or quadratically (P<0.05) enhanced the plasma concentration of GH, IGF-1 and insulin, which was significantly higher (P<0.05) in the DOW2 group than in the CON, DOW1 and DOW3 groups. In addition, the DOW treatment showed a lower (P<0.05) concentration of blood urea nitrogen (BUN) than the CON group. Replacing concentrate with DOW quadratically decreased (P<0.05) the ruminal ammonia nitrogen (NH3-N) and increased (P<0.05) the total of volatile fatty acids (TVFAs) at 0 and 4 h after feeding as well as linearly decreased (P<0.05) the NH3-N at 8 h after feeding. Replacing concentrate with DOW linearly decreased (P<0.05) the propionate and increased the aceate before feeding, and linearly decreased (P<0.05) propionate and quadratically increased (P<0.05) the aceate at 4 and 8 h after feeding. Lambs fed the DOW2 diet increased the phylum Firmicutes and genera Succiniclasticum and Ruminococcus_1 groups, whereas decreased (P<0.05) the relative abundance of phylum Deferribacteres and genera intestinimonas and Ruminiclostridium. In summary, replacing the concentrate with 15% DOW was beneficial for improving the rumen fermentation and ADG by increasing the DMI and modulating the rumen microbial community.

282 Metabolic and Endocrine Changes in Dairy Cows fed Different Diets at dry-off

Abstract Concentrate withdrawal and feed restriction reduce milk production to facilitate dry-off. We investigated the impact of feed rations providing different amounts of nutrients in combination with feed restriction on performance, endocrine, and metabolic responses before and after abrupt dry-off. Forty-three cows were studied from d 12 before until d 6 after dry-off (56 d before scheduled calving). Cows were fed experimental concentrates rich in either crude protein (nitrogenic, n=14), glucogenic precursors (glucogenic, n=14), or lipids (lipogenic, n=15). On d 3 before dry-off, total feed allowance was restricted to 50 % in one-half of the animals of each dietary group whereas feed allowance remained unchanged in the other animals. Statistical analysis (SAS, version 9.4) was carried out using a mixed model with dietary group, time, and diet×time interaction as fixed effects (Significance assumed at P&amp;lt; 0.05). Feed restriction immediately resulted in a negative energy balance (NEB) and decreased milk production (P&amp;lt; 0.05). Concomitantly, concentrations of non-esterified fatty acids (NEFA) increased, whereas insulin, insulin-like growth factor-1 (IGF-1), and glucagon decreased (P&amp;lt; 0.05). After dry-off, energy balance turned positive and plasma NEFA decreased again. Plasma glucose, insulin, and IGF-1 concentrations increased in all groups after dry-off. Glucose, insulin, and glucagon concentrations in plasma were greater in non-restricted compared with restricted animals after dry-off (P&amp;lt; 0.05). Milk and plasma urea concentrations were increased in cows fed the nitrogenic concentrate (P&amp;lt; 0.05). Overall, metabolic and endocrine adaptations supporting milk synthesis were continued during the first days after dry-off despite cessation of milking. Thus, the abrupt dry-off resulted in a short-term increase of glucose and triglyceride concentrations, with a delayed endocrine response to re-establish nutrient homeostasis in blood.

The correlation of serum/plasma IGF-1 concentrations with obstructive sleep apnea hypopnea syndrome: A meta-analysis and meta-regression.

BackgroundObstructive sleep apnea hypopnea syndrome (OSAHS) is a common disease that has serious cardiovascular and metabolic effects. Insulin-like growth factor 1 (IGF-1) levels are reportedly reduced in patients with OSAHS; however, this is still a matter of debate. Therefore, we investigated the association between serum/plasma IGF-1 levels and OSAHS in this meta-analysis.MethodsWan Fang, Excerpta Medica dataBASE, Web of Science, China National Knowledge Infrastructure, VIP, PubMed, and other databases were searched for materials published in any language before April 2, 2022. Two researchers analyzed the studies for quality according to the Newcastle-Ottawa Scale. The acquired data were analyzed using Stata 11.0 and R 3.6.1 software. The effect size was estimated and calculated using standard mean differences and correlation coefficients. Moreover, a combined analysis was conducted using either a random- or fixed-effects model.ResultsUltimately, 34 studies met our inclusion criteria. Our findings revealed that the plasma/serum IGF-1 concentrations in patients with OSAHS was significantly reduced compared with those in healthy subjects. Subgroup analyses were performed according to OSAHS severity, ethnicity, age, body mass index, specimen testing method, and study design. The outcomes suggested that nearly all subgroups of patients with OSAHS had reduced serum IGF-1 levels. Disease severity and differences in ethnicity were identified as possible influencing factors of serum IGF-1 levels in patients with OSAHS in the meta-regression analysis, and no other factors were found to alter plasma/serum IGF-1 concentrations. Moreover, plasma/serum IGF-1 concentrations were negatively correlated with apnea-hypopnea index and oxygen desaturation index scores and positively associated with minimum oxygen saturation.ConclusionSerum/plasma IGF-1 concentrations in patients with OSAHS were greatly reduced compared with those of patients in the control group, and were negatively correlated with apnea-hypopnea index and oxygen desaturation index scores and positively correlated with minimum oxygen saturation.Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022322738.

Pilot dose-ranging of rhIGF-1/rhIGFBP-3 in a preterm lamb model of evolving bronchopulmonary dysplasia.

Low levels of insulin-like growth factor-1 (IGF-1) protein in preterm human infants are associated with bronchopulmonary dysplasia (BPD). We used our preterm lamb model of BPD to determine (1) dosage of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) to reach infant physiologic plasma levels; and (2) whether repletion of plasma IGF-1 improves pulmonary and cardiovascular outcomes. Group 1: normal, unventilated lambs from 128 days gestation through postnatal age 5 months defined normal plasma levels of IGF-1. Group 2: continuous infusion of rhIGF-1/rhIGFBP-3 (0.5, 1.5, or 4.5 mg/kg/day; n = 2) for 3 days in mechanically ventilated (MV) preterm lambs determined that 1.5 mg/kg/day dosage attained physiologic plasma IGF-1 concentration of ~125 ng/mL, which was infused in four more MV preterm lambs. Group 1: plasma IGF-1 protein increased from ~75 ng/mL at 128 days gestation to ~220 ng/L at 5 months. Group 2: pilot study of the optimal dosage (1.5 mg/kg/day rhIGF-1/rhIGFBP-3) in six MV preterm lambs significantly improved some pulmonary and cardiovascular outcomes (p < 0.1) compared to six MV preterm controls. RhIGF-1/rhIGFBP-3 was not toxic to the liver, kidneys, or lungs. Three days of continuous iv infusion of rhIGF-1/rhIGFBP-3 at 1.5 mg/kg/day improved some pulmonary and cardiovascular outcomes without toxicity. Preterm birth is associated with rapid decreases in serum or plasma IGF-1 protein level. This decline adversely impacts the growth and development of the lung and cardiovascular system. For this pilot study, continuous infusion of optimal dosage of rhIGF-1/rhIGFBP-3 (1.5 mg/kg/day) to maintain physiologic plasma IGF-1 level of ~125 ng/mL during mechanical ventilation for 3 days statistically improved some structural and biochemical outcomes related to the alveolar formation that would favor improved gas exchange compared to vehicle-control. We conclude that 3 days of continuous iv infusion of rhIGF-1/rhIGFBP-3 improved some physiological, morphological, and biochemical outcomes, without toxicity, in mechanically ventilated preterm lambs.

Monensin supplementation during late gestation of beef cows alters maternal plasma concentrations of insulin-like growth factors 1 and 2 and enhances offspring preweaning growth

This study evaluated the effects of maternal prepartum supplementation of dried distillers grains (DDG), with or without monensin addition, on maternal performance and physiology and offspring preweaning growth. On day 0 (approximately 197 ± 4 d prepartum), 150 multiparous, Brangus crossbred beef cows were ranked by their initial body weight (BW; 524 ± 51 kg) and body condition score (BCS; 5.0 ± 0.63), and then randomly assigned into one of 15 bahiagrass (Paspalum notatum) pastures (10 cows and 8.1 ha/pasture). Maternal treatments were randomly assigned to pastures (5 pastures/treatment) and consisted of no prepartum supplementation of DDG (NOSUP) or supplementation of DDG at 1 kg/cow/d (dry matter basis; DM) added with 0 mg (SUP) or 200 mg/d of monensin (SUPMO) from days 0 to 77. Effects of maternal treatment and maternal treatment × day of the study were not detected (P ≥ 0.63) for any forage data. Cow BCS on day 35 and near calving (day 77) did not differ (P ≥ 0.19) between SUP and SUPMO cows but both groups had greater (P ≤ 0.001) BCS compared with NOSUP cows. Cow BCS at the start of the breeding season (day 142) and on day 168 were the greatest (P < 0.0001) for SUPMO cows, least for NOSUP cows, and intermediate (P ≤ 0.02) for SUP cows. Maternal plasma concentrations of glucose did not differ (P ≥ 0.25) among treatments. Plasma concentrations of insulin-like growth factor 1 (IGF-1) on day 77 were the least for NOSUP cows (P ≤ 0.05) and did not differ (P = 0.66) between SUP and SUPMO cows, whereas plasma concentrations of IGF-2 on days 35 and 77 were greatest (P ≤ 0.05) for SUPMO cows and did not differ (P ≥ 0.60) between NOSUP and SUP cows. Birth BW of first offspring did not differ (P = 0.77) between SUP and SUPMO calves but NOSUP calves were lighter at birth (P ≤ 0.05) compared with SUP and SUPMO calves. Percentage of cows pregnant with a second offspring did not differ (P = 0.72) between SUP and SUPMO cows and were the least for NOSUP cows (P ≤ 0.05). First offspring BW at weaning (day 325) was greatest (P ≤ 0.05) for SUPMO calves, least for NOSUP calves, and intermediate for SUP calves. Therefore, adding monensin into prepartum DDG supplements for Bos indicus-influenced beef cows did not increase cow prepartum BCS but led to greatest offspring preweaning growth, likely by modulating maternal plasma concentrations of IGF-1 and IGF-2 during gestation.

Effects of Short-term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans: The Role of Ghrelin in the Thrifty Phenotype.

A greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. As ghrelin and the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH, and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness. In 47 healthy individuals, 24hEE was measured in a whole-room indirect calorimeter both during 24-hour eucaloric and fasting conditions. Plasma total ghrelin, GH, and IGF-1 concentrations were measured by enzyme-linked immunosorbent assay after an overnight fast the morning before and after each 24-hour session. During 24-hour fasting, on average 24hEE decreased by 8.0% (P < .001), GH increased by ~5-fold (P < .001), whereas ghrelin (mean +23 pg/mL) and IGF-1 were unchanged (both P ≥ .19) despite a large interindividual variability in ghrelin change (SD 150 pg/mL). Greater fasting-induced increase in ghrelin was associated with a greater decrease in 24hEE during 24-hour fasting (r = -0.42, P = .003), such that individuals who increased ghrelin by 200 pg/mL showed an average decrease in 24hEE by 55 kcal/day. Short-term fasting induced selective changes in the ghrelin/GH/IGF-1 axis, specifically a ghrelin-independent GH hypersecretion that did not translate into increased IGF-1 concentrations. Greater increase in ghrelin after 24-hour fasting was associated with greater decrease in 24hEE, indicating ghrelin as a novel biomarker of increased energy efficiency of the thrifty phenotype.

Effects of Administering Exogenous Bovine Somatotropin During the First Trimester of Pregnancy Altered Uterine Hemodynamics in Suckled Beef Cows

The objective of this study was to examine the effects of recombinant bovine somatotropin (bST) administration on uterine hemodynamics and subsequent fetal programming in suckled cows during the first trimester of gestation. Crossbred beef cows (n = 152) were stratified by breed, days postpartum, parity, cyclicity status, and body condition score (BCS) before being assigned to either receive injections of bST every other week (BST; 500-mg/14 d) starting at fixed-time artificial insemination (TAI; d 0) until d 97 or to receive no bST (CTL). Blood samples were collected until d 97 for analysis of plasma concentrations of insulin-like growth factor 1 (IGF-1). Pregnancy was assessed via transrectal ultrasonography on d 41 and 173. A subset of pregnant cows (BST, n = 24; CTL, n = 28) were selected for assessment of uterine arterial blood flow (BF), pulsatility index, and resistance index (RI) of the uterine arteries ipsilateral and contralateral to the conceptus via color Doppler ultrasonography on d 97 and 233 of gestation. No differences (P = 0.99) were detected in body weight (BW) or BCS of dams; however, plasma concentrations of IGF-1 were greater (P &amp;lt; 0.001) in BST-treated cows. Color Doppler ultrasonography parameters differed whereby a treatment × day interaction (P = 0.007) was detected for RI on d 97 (P = 0.048); however, on d 233, RI did not differ (P &amp;gt; 0.10) but ipsilateral BF for BST-treated cows was greater (P = 0.0319) than controls. Mean heart girth diameter, crown-to-rump length, and neonate BW at 7 ± 5 d of calf age did not differ (P &amp;gt; 0.10). Liver tissue samples from each calf were collected for analysis of mRNA expression of target insulin-like growth factor system ligands. There was no difference in gene expression of hepatic IGF-1 between treatments (P = 0.99). A treatment × sex interaction was determined, where BST heifers had increased mRNA expression of IGFR1 compared to BST bulls (P = 0.03). Bi-weekly administration of bST until d 97 of pregnancy increased plasma concentrations of IGF-1, altered uterine hemodynamics in dams, induced sex-specific changes in liver gene expression of the offspring but failed to alter calf morphometries or calf performance until weaning.

Small for Gestational Age Preterm Neonates Exhibit Defective GH/IGF1 Signaling Pathway.

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates.Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60.Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml).Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

Copeptin and insulin-like growth factor-1 predict long-term outcomes after aneurysmal subarachnoid hemorrhage: A large prospective cohort study

ObjectiveThe predictive roles of copeptin and insulin-like growth factor-1 (IGF-1) in aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. We aimed to define the relationship between copeptin and IGF-1 levels and functional outcome as well as quality of life (QoL) after aSAH. MethodsPatients with aSAH were prospectively enrolled in a tertiary university hospital. Controls were sex- and age-matched healthy subjects. Plasma concentrations of copeptin and IGF-1 were measured on admission. Demographics and clinical, radiological and laboratory characteristics of the patients were collected. Favorable functional outcome was defined as modified Rankins≤2, and QoL was evaluated by the 36-Item Short Form Health Survey (SF-36) 1 year after aSAH. Uni- and multivariable analyses were performed. ResultsOne hundred eighteen patients were eligible, with 122 healthy controls were included in this study. Plasma copeptin levels were significantly higher and plasma IGF-1 was lower in patients than in controls. Both copeptin (adjusted HR 4.143 [1.120–15.328], p = 0.033) and IGF-1 levels (adjusted HR 0.089 [0.013–0.602], p = 0.013) were positively associated with 1-year mortality, while only single copeptin and IGF-1 concentrations were independent predictors of poor functional outcome and QoL, respectively. ConclusionsPlasma copeptin and IGF-1 levels are abnormal in patients with acute aSAH, and this may reliably predict long-term mortality, functional outcome and QoL.

The IGF-1/GH-GLUTs-plasma glucose regulating axis in hybrid grouper (Epinephelus fuscoguttatus♀ × epinephelus lanceolatus♂) fed a high-carbohydrate diet

The carnivorous teleost fish is often intolerant to high levels of postprandial plasma glucose. This study aimed to evaluate the effects of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) administrations on plasma glucose levels and expression of glucose transporters (GLUTs) in various tissues of hybrid grouper, and hence to further clarify the hormone-GLUTs-plasma glucose regulating axis. Twenty-four experimental fish (average body weight: 77.5 ± 5.4 g) were selected and injected with recombinant human IGF-1 (0.2 μg/g body weight) and PBS (0.01 mol/L) in enterocoelia, respectively, and in the GH injected experiment, the same quantity of fish (average body weight: 103.8 ± 5.8 g) were administrated with GH at a dose of 0.5 μg/g body weight or with PBS at a dose of 0.01 mol/L. Results showed that plasma glucose level was significantly (P < 0.05) declined by the IGF-1 administration but elevated by the GH administration. Plasma IGF-1 concentration was significantly (P < 0.01) elevated by the IGF-1 administration, while GH concentration did not significantly (P ≥ 0.05) respond to the GH administration. The relative mRNA levels of insulin-like growth factor-1 receptor a (IGF-Ra) in liver and muscle were decreased significantly with the IGF-1 administration, and a similar variation tendency was also found in insulin-like growth factor-1 receptor b (IGF-Rb) in liver, muscle and adipose tissues. Besides, the relative mRNA level of insulin receptor (IRS) in liver was significantly increased in the IGF-1 administrated group. After the GH administration, the mRNA levels of hepatic growth factor receptor 2 (GHR2) and IGF-1 were significantly elevated. As for GLUTs, the relative mRNA levels of GLUT1 and GLUT2 in liver were obviously elevated by the IGF-1 administration, while the mRNA level of GLUT4 in muscle was reduced. In liver, the protein levels of GLUT1, 2 and 4 were significantly elevated by the IGF-1 administration, and in adipose, only GLUT1 was observed to have a significantly increased protein level. The mRNA expression of GLUTs was less affected by the GH administration. The protein level of GLUT1 in liver was significantly reduced by the GH administration, while in adipose, it was significantly increased. The protein level of GLUT2 in liver or adipose showed an opposite variation as that of GLUT1. Overall, IGF-1 had a hypoglycemic effect on hybrid grouper, and this probably was through up-regulating the protein levels of hepatic GLUT1, 2 and 4 and adipose GLUT1. GH showed an opposite role in regulating plasma glucose level as IGF-1.

Evaluation of hypophysectomy for treatment of hypersomatotropism in 25 cats.

BackgroundSuccessful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats.ObjectivesTo describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020.AnimalsTwenty‐five client‐owned cats with spontaneous hypersomatotropism.MethodsRetrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin‐like growth factor‐1 (IGF‐1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF‐1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow‐up information from owners and referring veterinarians.ResultsMedian postoperative hospital stay was 7 days (range, 3‐18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0‐101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6‐13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF‐1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14‐240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900‐1794 days; range, 11‐3180 days) and the overall 1‐, 2‐, and 3‐year all‐cause survival rates were 76%, 76%, and 52%, respectively.Conclusions and Clinical ImportanceThis study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

Effects of administering exogenous bovine somatotropin to beef heifers during the first trimester on conceptus development as well as steroid- and eicosanoid-metabolizing enzymes.

The aim of this study was to evaluate the effect of bovine somatotropin (bST) on fetal and placental development during the first third of gestation in beef heifers. Angus heifers (n = 97) were randomly assigned to either receive a 500-mg injection of bST (BST) biweekly on days 0, 15, 29, 43, and 57 of gestation or not receive bST (CTL) throughout the experiment. Body weight (BW) was assessed on days -9, -3, 0, 15, 22, 29, 43, 50, 57, 64, and 77, while blood samples were collected on days 0, 22, 50, and 64. Pregnancy status was determined via transrectal ultrasonography on days 29 and 64. A subset of pregnant heifers (BST, n = 7; CTL, n = 5) were harvested on day 84, and complete gravid reproductive tracts and liver tissue were collected for analysis. Cytochrome P450 1A (CYP1A), 2C (CYP2C), 3A (CYP3A), and uridine 5'-diphospho-glucuronosyltransferase (UGT) activities were determined. Mean change in BW and average daily gain of heifers between fixed-time artificial insemination (day 0) and day 77 did not differ between treatments (P ≥ 0.05). Mean concentrations of insulin-like growth factor 1 (IGF-1) were greater (P < 0.001) in BST (347 ± 27.7 ng/mL) compared with CTL (135 ± 32.8 ng/mL) heifers. Mean placental weight, fetal membrane weight, uterine weight, and ovarian and corpus luteum (CL) weights, as well as fetal morphometric data, did not differ (P ≥ 0.05) between treatments. However, BST heifers had greater (P = 0.03) quantities of combined fetal fluid compared with CTL (521.6 ± 22.9 vs. 429.6 ± 27.14 g, respectively). Tendencies were observed for BST heifers to have reproductive tracts with fewer placentomes (P = 0.08) and fetuses with greater umbilical diameters (P = 0.09) compared with CTL. The activity of CYP1A did not differ (P ≥ 0.05) within the maternal and fetal liver, caruncle, cotyledon, or CL tissue samples between treatments. Furthermore, CYP3A activity was only observed in maternal liver samples and was not different between treatments (P ≥ 0.05). Interestingly, CYP2C activity was greater (P = 0.01) in the liver of BST vs. CTL heifers, and UGT activity was greater (P = 0.02) in the CL from BST heifers compared with CTL. In conclusion, the administration of bST during the first third of gestation increased plasma concentrations of IGF-1, which resulted in an increase in fetal fluid, decrease in placentome number, and greater umbilical diameter, but failed to alter fetal development.