Insulin-like Growth Factor-1 Concentrations Research Articles

Effects of gabapentin on slow-wave sleep period in critically ill adult patients: A randomized controlled trial.

Sleep deprivation is a prevalent problem in critically ill patients, which leads to delayed recovery and delirium. Slow-wave sleep (SWS) is essential to energy restoration, tissue repair, and immune system strengthening. This study aimed to investigate the effects of gabapentin on SWS in critically ill patients. We performed a prospective open-label randomized controlled study to compare SWS and the clinical outcomes of gabapentin versus a control intervention in critically ill adult patients admitted to the intensive care unit (ICU) within 24 h. The patients' characteristics and sleep-related outcomes were recorded. The sleep-related outcomes, namely, bispectral analysis (BIS), the Richards-Campbell Sleep Questionnaire (RCSQ), and insulin-like growth factor-1 (IGF-1) levels, were evaluated. Furthermore, clinical outcomes and safety were assessed. Sixty patients from 348 cases were eligible for randomization. On day 3 of the study, patients in the gabapentin group had significantly increased SWS (66.79 vs. 0.00 min; p < 0.001), total sleep time (TST) (331.39 vs. 46.16 min; p = 0.001), RCSQ score (55.05 ± 20.18 vs. 32.80 ± 15.31; p < 0.001), and IGF-1 concentrations (84.33 ± 12.40 vs. 44.00 ± 10.20 ng/mL, p < 0.001) compared with the control group. Improvements in clinical outcomes, such as delirium, ICU-free days, and mechanical ventilator-free days, were observed; however, these differences did not reach statistically significant. Gabapentin at bedtime increased SWS, TST, and IGF-1 concentrations in critically ill patients. This regimen might be beneficial to critically ill patients for improving their sleep quality.

Increased insulin-like growth factor 1 concentrations in a population of non-diabetic cats with overweight/obesity

Feline hypersomatotropism (HST) is typically associated with diabetes mellitus (DM), whereas HST without concurrent DM has only been reported in a few cases. Weight gain may be observed in cats with HST. The aims of this study were to evaluate circulating insulin-like growth factor-1 (IGF-1) in non-diabetic cats with overweight/obesity, to screen this population for the presence of HST, and to assess whether there is a correlation between body weight/body condition score (BCS) and serum IGF-1 concentration in overweight/obese cats. In this prospective study, 80 overweight/obese cats from referral centers in Buenos Aires (Argentina) were evaluated. Serum IGF-1 was measured as part of the routine tests for overweight/obesity. Non-diabetic cats were included in the study if they had a BCS>6/9. Twenty-nine cats were classified as overweight (BCS 7/9), whereas 51 were classified as obese (BCS 8-9/9). Median serum IGF-1 concentrations of cats with BCS 7/9, 8/9, and 9/9 were 570 ng/ml (range 123-1456 ng/ml), 634 ng/ml (range 151-1500 ng/ml), and 598 ng/ml (range 284-2450 ng/ml), respectively. There was a positive linear correlation between serum IGF-1 concentrations and body weight (r= 0.24, 95% CI 0.01-0.44 P=0.03), and between IGF-1 and BCS (r= 0.27, 95% CI 0.08-0.44 P=0.004). In total, 8.75% (95% confidence interval 3.6-17.2%) of the cats with overweight/obesity had IGF-1 concentrations >1000 ng/ml. Pituitary enlargement was detected on computed tomography in 4/7 cases. These seven cats showed varying degrees of phenotypic changes consistent with acromegaly. A proportion of 8.75 % of overweight/obese non-diabetic cats from referral centers in Buenos Aires had serum IGF-1 concentration in a range consistent with HST in diabetic cats. Likewise, 5% of overweight/obese cats were likely to be diagnosed with HST, supported by evidence of pituitary enlargement. Serum IGF-1 concentrations were positively correlated with body weight and BCS in this population of cats. This study highlights the relevance of screening different populations of non-diabetic cats to increase the detection of HST/acromegaly.

Differential Acute Adipogenic Signaling Changes Following Neuromusculoskeletal Injuries

Following traumatic injury, neuromusculoskeletal tissue undergoes extensive plastic modification. Changes can be observed at the local and systemic levels and can involve tissue function, signaling, and local composition. Currently there is limited understanding of early adipogenic changes following some traumatic injuries, which is needed to understand the long-term lack of functional muscle recovery. The objective of this project was to examine plasticity after injury, namely systemic and local adipogenic signaling and fat droplet deposition following volumetric muscle loss (VML) and denervation injuries. We hypothesized there would be differential changes in local and systemic adipogenic signaling, specifically changes in fat droplet accumulation following neuromusculoskeletal injuries. Adult C57B1/6J mice (n=36; 6 male, 6 female/group): posterior compartment VML, tibial nerve denervation, and naïve control. Both injury models target plantarflexor muscles. Mice were euthanized 72-hrs post-injury. In vivo muscle function was assessed, and gastrocnemius, liver, and serum were saved for analysis. Whole gastrocnemius muscles from a subset (n=4/group) were saved for histology, and five standardized sections were systematically obtained 1.5mm apart; muscle sections were stained with H&amp;E and Oil-Red-O to evaluate total fiber number and fat droplet accumulation, respectively. Data were analyzed by two- and three-way ANOVA with Tukey’s HSD post hoc. Maximal torque declined ~81 and 98% following VML and denervation injury, respectively (main effect p&lt;0.001), and VML-injured muscle was more fatigable than injury naïve (main effect p=0.001). Following denervation, liver insulin-like growth factor 1 (IGF-1) was increased ~52% compared to other groups, and was most pronounced in males (main effect injury p&lt;0.001; sex p=0.021). VML injury resulted in a 4-fold higher muscle IGF-1 regardless of sex (interaction p=0.021), and greater muscle interleukin-6 (IL-6), which was more pronounced in females (main effect injury p=0.001; sex p=0.049). Platelet-derived factor growth receptor (PDFGRα) expression was diminished following VML injury in both sexes (interaction p=0.016); suggesting a decrease in fibro-adipogenic progenitors (FAPs) and an alternative origin responsible for increases in IGF-1 and IL-6 rather than FAPs. Serum leptin concentrations were blunted following both VML- and denervation-injury (main effect p=0.002), which may illicit alterations in the regenerative process, specifically the maintenance of muscle quality. Serum IGF-1 and IL-6 concentrations were not affected by injury (p≥0.164). Histological analysis revealed a significant decrease in total fiber number across the middle three sections of the VML-injured muscle (i.e., the section initially injured) compared to other groups (p≤0.034). Findings provide a foundation for characterizing adipocyte development in the muscle remaining after injury and identify therapeutic targets for rehabilitative and nutritional approaches to address contractile and metabolic impairments following injury. Future work should elucidate the time course of adipogenic signaling following these injuries, with particular interest in their relationship to changes in metabolic and contractile impairments. R01-AR078903 (JAC &amp; SMG); University of Minnesota UROP (BAC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vitamin and mineral supplementation to beef heifers during gestation: impacts on morphometric measurements of the neonatal calf, vitamin and trace mineral status, blood metabolite and endocrine profiles, and calf organ characteristics at 30h after birth.

To examine the effects of feeding a vitamin and mineral supplement to beef heifers throughout gestation on mineral status and hormone/endocrine profiles in the dam and calf, and morphometric characteristics and organ mass of the calf at 30h after birth, Angus-based heifers (n = 72, 14 to 15 months of age, initial body weight [BW] = 380.4 ± 50.56kg) were estrus synchronized and artificially inseminated (AI) with female-sexed semen. Heifers were blocked by BW and randomly assigned to receive either a basal diet (CON; n = 36) or a basal diet plus a vitamin and mineral supplement (VTM; n = 36) via an individual feeding system beginning at breeding, with both diets targeting BW gains of 0.45kg heifer-1•d-1. Heifers not pregnant after first AI (CON, n = 19; VTM, n = 18) were re-bred via AI 60 d after treatment initiation, and heifers gestating female fetuses (CON, n = 7; VTM, n = 7) received treatments throughout gestation and were experimental units for this study. Calves were separated from their dams and fed colostrum replacer within 2h of birth and euthanized 30h after the first feeding. Calf morphometrics were recorded, and tissues were weighed and sampled. Serum from the dam at calving and serum, liver, and muscle from the calf at 30h were analyzed for concentrations of minerals. Serum from the dam and calf were analyzed for concentrations of leptin, vitamins A, D, and E, cortisol, growth hormone, and insulin-like growth factor 1. All response variables were analyzed using the MIXED procedure of SAS. Calf body morphometrics and BW of the dam at calving (P ≥ 0.32), calf organ weights (P ≥ 0.21), and calf ovarian follicle counts (P ≥ 0.13) were not affected by maternal treatment. Concentrations of Se and Co in calf serum and Se in calf liver were increased (P ≤ 0.02) in VTM. Serum concentrations of Co and vitamin A in the dam were greater (P ≤ 0.01) in supplemented compared with non-supplemented dams, and serum concentrations of vitamin D were greater (P ≤ 0.0003) in supplemented dams and calves compared with the non-supplemented cohort. Maternal supplementation supported vitamin and mineral status in the neonate, yet had no discernable impact on BW, organ mass, or circulating hormones/metabolites in the calf. Evaluating offspring at later postnatal time points is warranted to determine if prenatal vitamin and mineral supplementation affects performance, health, metabolism, and efficiency of energy utilization in key metabolic tissues in the calf.

The involvement of Akt, mTOR, and S6K in the in vivo effect of IGF-1 on the regulation of rat cardiac Na+/K+-ATPase.

We previously demonstrated that insulin-like growth factor-1 (IGF-1) regulates sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) in vascular smooth muscle cells (VSMC) via phosphatidylinositol-3 kinase (PI3K). Taking into account that others' work show that IGF-1 activates the PI3K/protein kinase B (Akt) signaling pathway in many different cells, we here further questioned if the Akt/mammalian target of rapamycin (mTOR)/ribosomal protein p70 S6 kinase (S6K) pathway stimulates Na+/K+-ATPase, an essential protein for maintaining normal heart function. There were 14 adult male Wistar rats, half of whom received bolus injections of IGF-1 (50μg/kg) for 24h. We evaluated cardiac Na+/K+-ATPase expression, activity, and serum IGF-1 levels. Additionally, we examined the phosphorylated forms of the following proteins: insulin receptor substrate (IRS), phosphoinositide-dependent kinase-1 (PDK-1), Akt, mTOR, S6K, and α subunit of Na+/K+-ATPase. Additionally, the mRNA expression of the Na+/K+-ATPase α1 subunit was evaluated. Treatment with IGF-1 increases levels of serum IGF-1 and stimulates Na+/K+-ATPase activity, phosphorylation of α subunit of Na+/K+-ATPase on Ser23, and protein expression of α2 subunit. Furthermore, IGF-1 treatment increased phosphorylation of IRS-1 on Tyr1222, Akt on Ser473, PDK-1 on Ser241, mTOR on Ser2481 and Ser2448, and S6K on Thr421/Ser424. The concentration of IGF-1 in serum positively correlates with Na+/K+-ATPase activity and the phosphorylated form of mTOR (Ser2448), while Na+/K+-ATPase activity positively correlates with the phosphorylated form of IRS-1 (Tyr1222) and mTOR (Ser2448). These results indicate that the Akt/mTOR/S6K signalling pathway may be involved in the IGF-1 regulating cardiac Na+/K+-ATPase expression and activity.

Effects of Growth Hormone-Releasing Hormone (GHRH) Plasmid Treatment on the Reproductive Productivity of Sows in Primiparous and Multiparous Sow Breeds.

The effect of growth hormone-releasing hormone (GHRH) plasmid treatment on sow reproductive performance was examined. Forty pregnant sows (three-way crossbreed: Landrace × Yorkshire × Duroc) at 85 days of gestation were included in the study and consisted of twenty primiparous and twenty multiparous sows (third parity). Sows were randomly assigned to the control and treatment groups. The treatment group received 5 mg dose of GHRH plasmid injection via electroporation, whereas the control group received a phosphate buffer solution. Reproductive indicators, including serum insulin-like growth factor-1 (IGF-1) concentration and weaned piglet data, were assessed. In the GHRH plasmid-treated group, serum IGF-1 concentration significantly increased compared with that in the control group, a trend observed in primiparous and multiparous sows. The key indicator of reproductive performance, litter size, showed that for control primiparous sows (C-PS), it was 10.90 ± 0.99 kg, while for control multiparous sows (C-MS), it was 14.00 ± 0.67 kg. Furthermore, for primiparous sows treated with GHRH plasmid (G-PS), the litter size was 11.60 ± 0.97 kg, and for multiparous sows treated with GHRH plasmid (G-MS), it was 14.00 ± 0.82 kg. The GHRH plasmid-treated group also exhibited a higher number of total births and surviving piglet numbers, along with a decrease in stillborn piglets; however, there was no significant difference in birth weight. The results suggest that GHRH plasmid treatment can enhance the reproductive performance of sows.

Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments

BackgroundChildren with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways.MethodsPlasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed.ResultsReduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3β, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females.ConclusionsSex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Insulin-like growth factor-1 and insulin-like growth factor binding protein-3 as early predictors of growth, body composition, and neurodevelopment in preterm infants.

To investigate the relationship between insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) and long-term growth, body composition, and neurodevelopment in preterm infants. Prospective data were collected from ≤32 weeks gestational age infant cohort (N = 50). IGF-1 and IGFBP-3 concentrations were measured at 1 week (early) and 35 weeks (late) post-menstrual age (PMA). Growth, body composition, and neurodevelopment outcomes were measured at 4 and 12 months PMA. Relationships were measured by linear regression analysis. Early IGFBP-3 concentration was positively associated with neurodevelopment at 12 months PMA. Early IGF-1 concentration was positively associated with weight at 4 months PMA, head circumference at 12 months PMA, and body mass index at 12 months PMA. Late IGFBP-3 concentration was positively associated with weight at 4 months PMA. Further investigation of these associations may lead to novel biomarkers and/or treatments to optimize health outcomes in preterm infants.

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.

Impact of dietary supplementation with β-alanine on the rumen microbial crude protein supply, nutrient digestibility and nitrogen retention in beef steers elucidated through sequencing the rumen bacterial community

This study investigated the effects of β-alanine (β-Ala) on rumen fermentation, nutrient digestibility, nitrogen (N) metabolism, plasma biochemical parameters, and rumen bacterial communities in beef steers. Six steers with initial liveweight of 252.8 ± 5.2 kg and 3 treatments of supplementing with 0, 30, or 60 g β-Ala per day to basal diet were allocated in a replicated 3 × 3 Latin square design. Each experimental period was 20 d, of which the first 15 d were for adaptation and the subsequent 5 d were for sampling. The results showed that β-Ala linearly increased the ruminal concentration of microbial crude protein (MCP) (P = 0.005), but it did not affect the ruminal concentrations of ammonia N and total volatile fatty acids (P > 0.10). β-Ala also linearly increased the dry matter (DM) (P = 0.009), organic matter (OM) (P = 0.017) and crude protein (CP) (P = 0.043) digestibility, tended to decrease the acid detergent fiber digestibility (P = 0.077), but it did not affect the neutral detergent fiber digestibility (P = 0.641). β-Ala quadratically increased the relative abundance of ruminal Bacteroidota (P = 0.021) at the phylum level, and increased Prevotella (P = 0.028) and Prevotellaceae_UCG-003 (P = 0.014), and decreased the relative abundance of NK4A214_group (P = 0.009) at the genus level. Feeding steers with β-Ala linearly increased the urinary N (P = 0.006), urea excretions (P = 0.002) and the N retention (P = 0.004), but it did not affect the N utilization efficiency (P = 0.120). β-Ala quadratically increased the plasma concentration of the total antioxidant capacity (P = 0.011) and linearly increased the plasma concentration of insulin-like growth factor-1 (P < 0.001). In summary, dietary supplementation with β-Ala improved the rumen MCP supply and increased the digestibility of DM, OM, CP and the N retention. Further research is necessary to verify the ruminal degradability of β-Ala and to investigate the mechanism of the impact of absorbed β-Ala on the anti-oxidative ability in steers.

Effects of dietary pectin on the growth performance, intestinal barrier, and antioxidant status of juvenile rainbow trout (Oncorhynchus mykiss)

To evaluate the effects of dietary pectin on growth performance, intestinal barrier, and antioxidant status of juvenile rainbow trout (Oncorhynchus mykiss), 10-week feeding trial was conducted. Five isoproteic and isoenergetic diets were formulated to contain 0% (P0), 4% (P4), 8% (P8), and 16% (P16) pectin as well as 0.02% pectinase (PE) at the expense of wheat starch, respectively. Dietary inclusion of 416% pectin linearly promoted the feed intake and growth performance but depressed the feed efficiency, but significant differences were only observed between the P16 and P0 groups. Similarly, dietary inclusion of 816% pectin significantly increased the foregut trypsin and amylase activities but decreased the foregut and midgut sucrase activity. The midgut muc2 gene expression level was significantly down-regulated by the inclusion of 16% pectin. Dietary inclusion of 2% pectin increased the abundance of Proteobacteria and Stenotrophomonas but reduced the abundance of Actinobacteria, Bacteroides and Helicobacter; while the lowest values of observed species, Chao1 and ACE indices of intestinal flora were found in the P8 group. Fish fed with the P8 diet exhibited the lowest plasma catalase and midgut glutathione S-transferase activities as well as malondialdehyde content, but the highest midgut malondialdehyde content. Dietary inclusion of 816% pectin significantly depressed the plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and mechanistic target of rapamycin contents as well as alanine aminotransferase activity, the hepatic adenosine monophosphate deaminase and glutamate dehydrogenase (GDH) activities. Dietary treatment with 0.02% pectinase did not affect the growth performance, but depressed the foregut sucrase activity, the midgut amylase and sucrase activities, increased the plasma GH and IGF-1 contents as well as hepatic GDH and aspartate aminotransferase activities. In conclusion, high-dose of dietary pectin (816%) may promote the feed intake and intestinal digestive enzyme activities and thereby improve the growth performance of rainbow trout.

GH and IGF-1 in skin interstitial fluid and blood are associated with heat loss responses in exercising young adults.

Sweat glands and cutaneous vessels possess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) receptors. Here, we assessed if exercise increases GH and IGF-1 in skin interstitial fluid, and whether baseline and exercise-induced increases in GH and IGF-1 concentrations in skin interstitial fluid/blood are associated with heat loss responses of sweating and cutaneous vasodilation. Sixteen young adults (7 women) performed a 50-min moderate-intensity exercise bout (50% VO2peak) during which skin dialysate and blood samples were collected. In a sub-study (n = 7, 4 women), we administered varying concentrations of GH (0.025-4000ng/mL) and IGF-1 (0.000256-100µg/mL) into skin interstitial fluid via intradermal microdialysis. Sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC) were measured continuously for both studies. Exercise increased sweating and CVC (both P < 0.001), paralleled by increases of serum GH and skin dialysate GH and IGF-1 (all P ≤ 0.041) without changes in serum IGF-1. Sweating was positively correlated with baseline dialysate and serum GH levels, as well as exercise-induced increases in serum GH and IGF-1 (all P ≤ 0.044). Increases in CVC were not correlated with any GH and IGF-1 variables. Exogenous administration of GH and IGF-1 did not modulate resting sweat rate and CVC. (1) Exercise increases GH and IGF-1 levels in the skin interstitial fluid, (2) exercise-induced sweating is associated with baseline GH in skin interstitial fluid and blood, as well as exercise-induced increases in blood GH and IGF-1, and (3) cutaneous vasodilation during exercise is not associated with GH and IGF-1 in skin interstitial fluid and blood.

Abstract B082: A pro-tumorigenic, aged microenvironment may aid in worsened disease progression in an HGSOC model

Abstract Over 70% of HGSOC patients are diagnosed after 55 and the average patient succumbs to disease at 70 years old. Despite this, most ovarian cancer research, and cancer studies generally, utilize young mice that are mimetic of human teenagers and/or do not investigate age as a variable despite it being the top cancer risk factor. An improved understanding of how age affects HGSOC progression may enable development of alternative treatment strategies aimed at intercepting metastasis and preventing cancer cells from establishing in the peritoneum. Our preliminary studies show tumor burden and disease severity are significantly higher in aged versus young animals. We developed an epithelial cell line derived from C57Bl/6 oviducts and used CRISPR-Cas9 genome editing to develop a syngeneic tumorigenic line harboring Trp53, Pten, and Brca2 deletions. After intraperitoneal injection into 6-week and 14-month-old immunocompetent C57Bl/6 mice, we observed a stark increase in tumor burden in aged mice. Furthermore, older mice died at a faster rate; all aged mice succumbed to disease within 1-month of inoculation compared to young mice surviving up to 3 months. Total RNA-sequencing of tumors harvested from aged and young mice is ongoing. Characterization of the tumor-naïve peritoneal compartment revealed the aged microenvironment to be highly inflammatory. When assessed via cytokine array, peritoneal fluid of aged mice had higher concentrations of inflammatory markers including soluble TNF receptor-1 (sTNFR-1), L-selectin, and VCAM-1. Flow cytometry of peritoneal lavage indicated an over 2-fold increase in the number CD45+ cells present in the peritoneal cavity, coinciding with cytokine array results. Within this population, there was nearly complete depletion of macrophage and neutrophil populations and a significant increase in B cells and CD4+ and CD8+ T cells. The percentage of PD-1+ CD8+ cells also increased. In addition to increased signs of inflammation, a significantly higher concentration of insulin-like growth factor-1 (IGF-I) and higher concentrations of the associated IGF binding proteins -3 and -6 were found in peritoneal fluid of aged mice. In addition, during tissue collection, organs of the aged mice were found to be much larger than young mice, a common effect of elevated IGF-I; aged omentum weighed 2-4 times that of young. Notably, IGF-I is known to inhibit apoptosis and promote proliferation and increased IGF-I is correlated with increased risk of breast, prostate, and lung cancer. A drastic difference in disease severity occurs when identical cancer cells are injected into 6-week and 14-month-old mice. To identify possible microenvironmental differences in the two populations, a broad panel of cytokines was assessed, and immune populations were quantified in pre-cancerous mice. Overall, multiple pro-inflammatory markers and the number of lymphocytes were upregulated in the aged peritoneal cavity, and markers of immune fatigue were present. Further work is aimed at identifying immune cell state via further cytometry and sequencing. Citation Format: Katherine A. Cummins, Ronny I. Drapkin, Matthew Knarr. A pro-tumorigenic, aged microenvironment may aid in worsened disease progression in an HGSOC model [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B082.

Post-COVID syndrome: status of carbohydrate metabolism in patients with hypertension and stable ischemic heart disease

Background. Post-COVID syndrome is associated with a wide range of chronic symptoms or conditions. Coronavirus di­sease 2019 (COVID-19) causes metabolic disorders such as hyperglycemia, insulin resistance. Insulin-like growth factor 1 (IGF-1) is associated with an impaired glucose tolerance and a higher risk of developing type 2 diabetes. Currently, the study of molecules regulating carbohydrate metabolism as potential biomarkers of post-COVID syndrome and targets for therapeutic influence is relevant. The purpose of the study was to assess the level of IGF-1 and its relationship with regulation of carbohydrate metabolism, as well as the dynamics of the evaluated indicators under the influence of drug treatment in patients with hypertension and stable coronary heart disease who suffered from COVID-19. Materials and methods. Fifty-five patients who had a mild and moderate COVID-19 were included in the study; their average age was 55.87 [40; 75] years. The results of routine laboratory tests were registered and analyzed. The content of insulin and IGF-1 was assessed by enzyme immunoassay. The HOMA-IR was calculated. Results. In patients with a mode­rate COVID-19 compared to those with a mild one, a significant decrease in the level of IGF-1 (р = 0.008) was found against the background of increased reference values of glucose, insulin, and HOMA-IR (р &lt; 0.01). The influence of the degree of hypertension on the IGF-1 level was revealed (р = 0.004). An inverse relationship between IGF-1 and glucose level was noted (r = –0.28, p = 0.034). The use of meldonium contributed to a significant decrease in glucose and insulin content (p &lt; 0.001), and an increase in IGF-1. Against the background of taking meldonium, the dynamics of the shift towards a decrease in the HOMA-IR was more significant. Conclusions. An inverse relationship was found between IGF-1 and blood glucose, regardless of the level of insulin and HOMA-IR, in patients with hypertension and stable ischemic heart disease in the post-COVID period. Meldonium has been shown to improve carbohydrate metabolism by normalizing insulin levels and redu­cing the phenomena of insulin resistance as a potential drug target. Meldonium improved the clinical course of ischemic heart disease and demonstrated good tolerability and safety.

Energy-Related Hormones in Raw and Retail Cow’s Milk and Possible Risk for Consumers

Abstract The study aimed to determine the concentration of energy-related hormones in cow’s milk and to consider them from a public health perspective. Fourteen Holstein cows were subjected to milk and blood sampling on the following days in lactation (DIL): 10, 30, 60, 90, 150, 180, 210, 250 and 280 to determine milk hormones, fat and protein content and blood biochemical parameters. For the same purpose, bulk-tank milk was sampled and samples of retail m ilk with 1.5% (CM1.5) and 3.2% (CM3.2) fat was purchased. Milk insulin-like growth factor-1 (IGF-1) values were significantly lower at 90, 150, 180, 210 and 250 and significantly higher at 10, 30 and 60 DIL than lactation average (LA). Milk insulin concentrations were significantly lower at 30, 60 and 90 and higher at 210, 250 and 280 DIL than LA. Free thyroxine (fT4) level in the milk was higher at 250 DIL, while milk free triiodothyronine (fT3) concentrations were lower at 30, 60, 90 and 280 DIL, and significantly higher at 10 and 180 DIL than respective LA. Milk cortisol levels were lower at 60 and 280 DIL than LA. All measured milk hormones were significantly lower in CM1.5 compared to CM3.2, bulk-tank milk and LA. An exception was the LA of IGF-1, which was significantly lower than the IGF-1 content in CM1.5. Blood biochemical parameters fluctuated evenly during lactation and were within the reference range. Hormone concentrations in cow’s milk fluctuate during lactation, giving milk an important role in the context of public health.

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.

Effects of glycyrrhiza polysaccharides on growth performance, meat quality, serum parameters and growth/meat quality-related gene expression in broilers.

With growing restrictions on the use of antibiotics in animal feed, plant extracts are increasingly favored as natural feed additive sources. Glycyrrhiza polysaccharide (GP), known for its multifaceted biological benefits including growth promotion, immune enhancement, and antioxidative properties, has been the focus of recent studies. Yet, the effects and mechanisms of GP on broiler growth and meat quality remain to be fully elucidated. This study aimed to investigate the effects of GP on growth, serum biochemistry, meat quality, and gene expression in broilers. The broilers were divided into five groups, each consisting of five replicates with six birds. These groups were supplemented with 0, 500, 1,000, 1,500, and 2,000 mg/kg of GP in their basal diets, respectively, for a period of 42 days. The results indicated that from day 22 to day 42, and throughout the entire experimental period from day 1 to day 42, the groups receiving 1,000 and 1,500 mg/kg of GP showed a significant reduction in the feed-to-gain ratio (F:G) compared to the control group. On day 42, an increase in serum growth hormone (GH) levels was shown in groups supplemented with 1,000 mg/kg GP or higher, along with a significant linear increase in insulin-like growth factor-1 (IGF-1) concentration. Additionally, significant upregulation of GH and IGF-1 mRNA expression levels was noted in the 1,000 and 1,500 mg/kg GP groups. Furthermore, GP significantly elevated serum concentrations of alkaline phosphatase (AKP) and globulin (GLB) while reducing blood urea nitrogen (BUN) levels. In terms of meat quality, the 1,500 and 2,000 mg/kg GP groups significantly increased fiber density in pectoral muscles and reduced thiobarbituric acid (TBA) content. GP also significantly decreased cooking loss rate in both pectoral and leg muscles and the drip loss rate in leg muscles. It increased levels of linoleic acid and oleic acid, while decreasing concentrations of stearic acid, myristic acid, and docosahexaenoic acid. Finally, the study demonstrated that the 1,500 mg/kg GP group significantly enhanced the expression of myogenin (MyoG) and myogenic differentiation (MyoD) mRNA in leg muscles. Overall, the study determined that the optimal dosage of GP in broiler feed is 1,500 mg/kg.

Changes in Techno-Functional Characteristics of Cow Colostrum Powder Prepared by Freeze Drying

The present study investigates the characteristics of freeze-dried bovine colostrum powder prepared from the first three milkings of Karan fries cattle at different intervals. Bioactive components of bovine colostrum are heat sensitive, and therefore, in order to retain the biological activity of different components, it should be subjected to minimal nonthermal treatment. In this study, the optimum temperature/time combination of 60°C/45 min was used for the processing of cow colostrum. At this temperature, the microbial count significantly decreased as compared to raw colostrum. In freeze-dried bovine skimmed colostrum powder (BSCP) and bovine colostrum whey powder (BCWP), IgG emerged as the highest fraction among immune factors, whereas in growth factors, insulin-like growth factor 1(IGF1) and transforming growth factor β2 (TGFβ2) were found in large proportion as compared to insulin-like growth factor 2 (IGF2) and transforming growth factor β1 (TGFβ1). The IgG content (per 100 g) of BSCP prepared from 1st, 2nd, and 3rd milking was found to be 36.62, 27.87, and 20.51 g, respectively, whereas IgG content (per 100 g) of BCWP prepared from 1st, 2nd, and 3rd milking was found to be 33.32, 24.53, and 16.81 g, respectively. The IGF1 content (per 100 g) of BSCP prepared from 1st, 2nd, and 3rd milking was found to be 921.6, 741.2, and 617.2 μg, respectively, whereas IGF1 content (per 100 g) of BCWP prepared from 1st, 2nd, and 3rd milking was found to be 869.8, 688, and 454.4 μg, respectively. The TGFβ2 content (per 100 g) of BSCP prepared from 1st, 2nd, and 3rd milking was found to be 1278, 1076, and 856.8 μg, respectively, whereas TGFβ2 content (per 100 g) of BCWP prepared from 1st, 2nd, and 3rd milking was found to be 1167, 950.2, and 769.2 μg, respectively. The microstructure of freeze-dried cow colostrum whey powder revealed that its pore size was more than that of skimmed colostrum powder. BCWP exhibited lower phagocytic activity as well as lymphocyte proliferation index as compared to BSCP which was carried out in vitro. The observations of the study provide an insight about the components present in BCWP and BSCP apart from the physical characteristics of the products which might pave the way for its utilization in various food formats.

Mating Season Influences Placental Characteristics, Plasma IGF Concentration, and mRNA Expression without Affecting Lamb Birth Weight in Akkaraman Ewes

Seasonal variations significantly impact lambs’ birth weight and post-natal growth of lambs, yet the underlying physiological mechanisms remain insufficiently explored. Therefore, this study examined the effects of mating season on lamb birth weight, placental characteristics, maternal concentrations of insulin-like growth factors (IGFs) in plasma, and placental mRNA expression levels of IGFs in Akkaraman ewes reared under extensive conditions. Ewes were mated in the breeding season (September; n = 35) and out-of-breeding season (April; n = 27). Blood samples were taken from the jugular vein of all ewes using a vacutainer in sterile heparin tubes every month from mating to parturition. Post-lambing, both dam and lamb weights were recorded, and placental characteristics were documented within 12 hours of parturition in both seasons. The number and weight of cotyledons were higher (P&lt;0.05) in ewes mated during the breeding season than those mated during the out-of-breeding season. Also, ewes mated during the breeding season demonstrated thicker large cotyledons (P&lt;0.05). Although placental and cotyledonal efficiencies were similar in both mating seasons, volumetric cotyledon efficiency was higher (P&lt;0.05) in ewes mated during the out-of-breeding season than in those bred during the breeding season. Additionally, ewes mated in the breeding season exhibited higher plasma concentration of IGF-I at three months of gestation than ewes mated in the out-of-breeding season (123.8 ± 9.8 vs. 99.3 ± 11.4 ng/ml, respectively; P&lt;0.05). Although the mating season did not affect the IGF-I gene’s placental mRNA expression levels, the IGF-II gene’s expression level was notably higher (P&lt;0.05; fold change: 2.84) in ewes mated during the breeding season. The results suggest that mating season influences placental characteristics, maternal plasma IGF-I concentrations, and IGF-II gene expression levels of cotyledons due to alterations in cotyledon numbers and size on the surface of the placenta.

Utility of insulin-like growth factor-1 (IGF-1) in growth hormone-treated short children – An experience from a tertiary level center

Introduction: Very few studies have been conducted in low-middle-income countries to assess the response to growth hormone (GH) therapy by measuring the improvement in insulin-like growth factor-1 (IGF-1) concentrations. Objectives: The objective is to assess IGF-1 concentrations in patients receiving GH therapy to correlate the height increment with respect to increase in the IGF-1 concentrations, including IGF-1 Z-scores as a measure of safety profile. Methods: Clinical and anthropometric data were extracted retrospectively from hospital records of children aged 0–18 who received GH and had IGF-1 measured during the study period. Serum IGF-1 concentrations were analyzed by a solid-phase enzyme-linked immunosorbent assay. Patients with GH deficiency (GHD) and multiple pituitary hormone deficiency (MPHD) were grouped as group A, while participants receiving GH therapy for non-GHD/MPHD were clubbed as group B. Results: We report a significant positive correlation between an increase in IGF-1 values and increase in height. The improvement in height Z-scores was significantly higher in participants of group A as compared to B, with no significant difference in increase in IGF-1 Z-scores between the two groups. A total of 18.75% of subjects had IGF-1 Z-scores between +2 and +3, and these were largely subjects belonging to group B. Conclusion: The increment in height and height velocity Z-scores in the patients on GH correlated with increase in the IGF-1 concentrations, particularly in GHD/MPHD group of patients.