Insulin-like Growth Factor-1 Gene Expression Research Articles

Modulation of toxic effects of ammonia on growth, pathology of liver and kidney tissues and relative expression of GH and IGF-1 Genes by CoQ10 Supplementation in Oncorhynchus mykiss.

Reducing the negative impact of environmental and stressful factors is a crucial step in achieving sustainable aquaculture. Therefore, a study was aimed at evaluating the impacts of Coenzyme Q10 (CoQ10) supplementation on growth, relative gene expression of Growth Hormone (GH) and Insulin-like growth factor-1 (IGF-1), liver and kidney histopathology against stress induced by ammonia in Rainbow trout (Oncorhynchus mykiss). The fish were given feed containing different levels of CoQ10 for 8 weeks: Control - CoQ10 0%, G1 - CoQ10 0.1%, G2 - CoQ10 0.5% and G3 - CoQ10 1%. At the end of the experiment, fish were exposed to ammonia stress concentration at 0.6mg/L for 24 h to assess liver and kidney tissue damage. Results showed that there was a significant activity increase in GH and IGF-1 genes due to supplementation with CoQ10 alone (p < 0.05). Gene expression for GH increased about two-fold whereas that for IGF-1 experienced a four-fold upregulation compared to controls (p < 0.05). CoQ10's-related antioxidant effects probably minimized liver and kidney cellular injuries, as significant decreases were observed in ammonia-induced mortality (p < 0.05). In summary, adding CoQ10 to the diet is a potential way to improve fish production through controlling the gene expression of GH and IGF-1, as well as making fish populations more resistant to possible future stress caused by ammonia in intensive or super-intensive aquaculture systems.

Dietary chromium-methionine supplementation and broiler (22–43 days) responses during heat stress. 2 - Physiological variables, and heat shock protein 70 and insulin-like growth factor-1 gene expression

Dietary chromium-methionine supplementation and broiler (22–43 days) responses during heat stress. 2 - Physiological variables, and heat shock protein 70 and insulin-like growth factor-1 gene expression

Effect of duration of estradiol exposure on embryo survival and endometrial gene expression in anestrous embryo recipient mares

Previous studies indicate a positive correlation between the duration of estrus prior to ovulation and likelihood of pregnancy in embryo recipient mares. However, the mechanisms by which the duration of estrus before may affect fertility remains unclear. This study aimed to determine the effect of different durations of estradiol exposure, prior to progesterone administration, on embryo viability in anestrous recipient mares, and endometrial expression of genes thought to influence embryo survival. Three groups of anestrous recipient mares treated with different duration of estradiol were used: long (LE), short (SE) and no treatment (NE). Day 8 embryos were transferred into recipient mares four days after long-acting progesterone administration and recovered 48h later to examine embryo growth and viability. The endometrial gene expression profile of selected genes was also investigated. The likelihood of recovering an embryo 48h after transfer was 46.1% (6/13), 62.5% (5/8) and 85.7% (6/7) for recipient mares from the NE, SE and LE groups, respectively (P = .09). Embryos recovered from the different groups of recipients did not, however, differ in size, morphology or the proportion of nuclei undergoing mitosis (P > .05). Abundance of mRNA for uterocalin (P19) and insulin-like growth factor 1 (IGF1) were increased in the LE compared to the NE group, while fibroblast growth factor 2 (FGF2), progesterone receptor (PGR) and insulin-like growth factor 1 receptor (IGF1R) transcript abundances were increased (P < 0.05) in the NE group compared to both SE and LE groups. In conclusion, a longer exposure of the endometrium to estradiol before progesterone tended to improve embryo survival within 48h of transfer. However, the grade, growth rate, and proportion of mitotic cells in surviving embryos did not differ among groups. If embryos are destined to fail in a suboptimal endometrial environment, they die and disappear quickly. Moreover, a more adequately estradiol-primed uterus, before the progesterone rise, seems to create a uterine environment, in terms of P19, IGF1, FGF2 and PGR gene expression, more conducive to embryo survival and further development.

Ostarine blunts the effect of endurance training on submaximal endurance in rats

The purpose of this study is to study the effects of ostarine alone and in combination with endurance training in sexually mature, male Wistar rats. The rats were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8 weeks (n = 10 each, in total n = 40). We examined some functional, hormonal, and anthropometric parameters and the myogenic gene expression of myostatin, insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor-A (VEGF-A) in m. gastrocnemius. Ostarine decreased submaximal endurance and increased myogenic gene expression of myostatin but had no effect on maximal time to exhaustion and grip strength. Training increased submaximal endurance, maximal time to exhaustion, and grip strength. Our results indicate that both exercise and ostarine treatment had no significant effects on serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone, or on the myogenic gene expression of IGF-1 and VEGF-A. Neither ostarine nor the training had a significant effect on the testis, liver, and heart weights. In conclusion, ostarine had no effect on anthropometric and hormonal parameters but increased the myostatin gene expression in muscle. The SARM treatment decreased submaximal endurance without affecting maximal time to exhaustion, and training increased both metrics.

Effects of feeding diets with zinc-l-selenomethionine on growth performance of broilers subjected to cyclic heat stress.

Limited information exists on the use of zinc-l-selenomethionine (Zn-L-SeMet) in broiler diets and its effects on the growth performance, body temperature, mortality rates, blood profile, and gene expression, especially when animals are reared under cyclic heat stress conditions. This study aimed to investigate the impact of Zn-L-SeMet in broiler diets from 1 to 42days of age reared under cyclic heat stress and its effects on growth performance, cloacal temperatures, mortality rate, blood parameters, and insulin-like growth factor 1 (IGF-1) and growth hormone receptor (GHR) gene expression in the breast muscle. A total of 1000 male Cobb 500® broiler chicks were randomly assigned to five treatments: 0, 0.15, 0.23, 0.47, and 1.30mg/kg of Zn-L-SeMet. Each treatment consisted of 10 replicates with 20 birds each. No statistically significant differences in growth performance were observed from 1 to 21days of age (P > 0.05). However, from 1 to 42days, feed intake (FI) and feed conversion ratio (FCR) decreased linearly (P < 0.05). Cloacal temperatures showed no significant effects (P > 0.05), while overall mortality rate exhibited a quadratic response (P < 0.05), with the optimal inclusion level predicted to reduce broiler mortality at 0.71mg/kg. Triglyceride (TRG) levels increased with 0.97mg/kg (P < 0.05), and gama-glutamil transferase (GGT) levels decreased with the inclusion of 1.19mg/kg (P < 0.05). No significant effects on IGF-1 and GHR gene expression were found (P > 0.05). In conclusion, the inclusion of 1.30mg/kg of Zn-L-SeMet in diets of heat-stressed broilers improved growth performance from 1 to 42days of age. An inclusion of 0.71mg/kg reduced mortality rate, while 0.97mg and 1.19mg increased and reduced TRG and GGT levels, respectively.

Positive effects of dietary Clostridium butyricum supplementation on growth performance, antioxidant capacity, immunity and viability against hypoxic stress in largemouth bass.

The effects of dietary supplementation of Clostridium butyricum (CB) on growth performance, serum biochemistry, antioxidant activity, mRNA levels of immune-related genes and resistance to hypoxia stress were studied in largemouth bass. Feed with CB0 (control, 0 CFU/kg), CB1 (4.3×108 CFU/kg), CB2 (7.5×108 CFU/kg), CB3 (1.5×109 CFU/kg) and CB4 (3.2×109 CFU/kg) CB for 56 days, and then a 3h hypoxic stress experiment was performed. The results showed that dietary CB significantly increased the WGR (weight gain rate), SGR (specific growth rate), PDR (protein deposition rate) and ISI (Intestosomatic index) of largemouth bass (P<0.05). Hepatic GH (growth hormone)/IGF-1 (insulin-like growth factor-1) gene expression was significantly upregulated in the CB3 and CB4 groups compared with the CB0 group (P<0.05), while the FC (feed conversion) was significantly decreased (P<0.05). Serum TP (total protein) and GLU (glucose) levels were significantly higher in the CB4 group than in the CB0 group (P<0.05), while the contents of serum AST (aspartate transaminase), ALT (alanine transaminase), AKP (alkline phosphatase) and UN (urea nitrogen) in CB4 were significantly lower than those in CB0 (P<0.05). T-AOC (total antioxidant capacity), SOD (superoxide dismutase), CAT (catalase), POD (peroxidase) and GSH-Px (glutathione peroxidase) activities were significantly higher in CB3 and CB4 groups than in CB0 group (P<0. 05). The liver MDA (malondialdehyde) content of CB1, CB2, CB3 and CB4 groups was significantly higher than that of CB0 group (P<0. 05). The relative expressions of IL-1β (interleukin 1β), TNF-α (tumor necrosis factor α) and TLR22 (toll-like receptor-22) genes in CB2, CB3 and CB4 groups were significantly lower than those in CB0 group (P<0.05). The relative expression of IL-8 (malondialdehyde) and MyD88 (Myeloid differentiation factor 88) genes in the CB4 group was significantly lower than that in the CB0 group (P<0.05). The liver LZM (lysozyme) content of CB2, CB3 and CB4 groups was significantly higher than that of CB0 group (P<0. 05). The relative expression of IL-10 (interleukin 10) and TGF-β (transforming growth factor β) genes in the CB4 group was significantly higher than that in the CB0 group (P<0.05). Under hypoxic stress for 3h, the CMR of CB0 group was significantly higher than that of CB1, CB2, CB3 and CB4 groups (P<0.05). Dietary CB can improve the growth performance and resistance to hypoxic stress of largemouth bass by regulating the expression of GH/IGF-1 gene and inflammatory factors and inhibiting TLR22/MyD88 signaling pathway.

Screening the Chemical Composition and Bioactivity of Cerasus serrulata Flower Extracts Using Two Extraction Methods

Background Cerasus serrulata has an excellent antioxidative, antibacterial, and anti-alopecia effect, but its active ingredients and the underlying mechanism are currently unclear, in addition to the fact that the active products vary with the extraction methods. Aim Therefore, this study aims to clarify the active components and antioxidative property of C. serrulata extracted by two different methods (low-temperature vacuum extraction and ethanol extraction) and explore its potential biofunction. Materials and Methods First, the compositions in extracts were characterized by gas chromatographic mass spectrometry (GC-MS) and liquid chromatography-mass spectrography (LC-MS). Then, the antioxidative activity of both extracts was evaluated using free radical scavenging assay (ABTS) and ORAC. Next, the antibacterial activity of both extracts was measured via a bacteriostatic circle experiment. The anti-alopecia effects of both extracts were studied using a mouse model of alopecia. The hematoxylin and eosin (H&amp;E) staining was used to evaluate hair follicles; vascular endothelial-derived growth factor (VEGF) and interleukin-6 (IL-6) expression in mouse skin were evaluated by immunohistochemistry, while β-catenin expression in tissues was used by immunofluorescence. The expression of FGFR and insulin-like growth factor 1 (IGF-1) in the skin was determined to evaluate using real-time quantitative polymerase chain reaction (RT-qPCR). The levels of DHT and 5α-reductase in the experimental mice were determined by ELISA. Results The GC-MS analysis results showed that the extracts were rich in alkanes and aromatic compounds, specifically benzaldehyde, which was the highest component in the cold vacuum extraction, while pipecolic acid was the main component in the ethanol extract. This indicates that C. serrulata has components that exhibit strong inhibitory ability against the growth of five common bacterial strains, expressing excellent free radical scavenging ability. In addition, the active ingredients in C. serrulata were found to significantly deregulate the protein levels in the skin of androgenetic alopecia (AGA) mice, with the levels of IL-6. They were also able to significantly inhibit VEGF reduction. The β-catenin was being significantly upregulated in skin tissue. In addition, FGFR and IGF-1 gene expression also increased. The 5α-reductase and dihydrotestosterone (DHT) can be reduced in the C. serrulata treatment. Conclusion Our data indicate that C. serrulata extract could be beneficial supplements of natural antioxidative, antibacterial, and anti-alopecia agents.

The effects of weight bearing on muscle atrophy early after ACL reconstruction in rats

We examined the effects of weight bearing after anterior cruciate ligament (ACL) reconstruction on muscle atrophy in rats. Rats were divided into the following groups: untreated control, ACL reconstruction (amount of weight bearing was small), ACL reconstruction plus hindlimb unloading (nonweight bearing), and ACL reconstruction plus morphine administration (amount of weight bearing was large) groups. At 7 or 14 days after surgery, atrophy of the rectus femoris and gastrocnemius was assessed. ACL reconstruction induced muscle atrophy in the rectus femoris and gastrocnemius. Unloading facilitated atrophy in the gastrocnemius but not in the rectus femoris. Morphine administration partially prevented atrophy in the gastrocnemius but not in the rectus femoris. After ACL reconstruction, the gene expression of insulin-like growth factor-1 (IGF-1), which is involved in protein synthesis, was downregulated in the gastrocnemius. Unloading decreased the gene expression of IGF-1 and increased the gene expression of atrogin-1, which is involved in protein breakdown, in the gastrocnemius. Morphine administration attenuated the downregulation of IGF-1. Atrophy of the gastrocnemius was more severe with a decrease in weight bearing, although the effect of weight bearing on rectus femoris atrophy was limited in rats. Early weight bearing is effective for reducing gastrocnemius muscle atrophy after ACL reconstruction.

Oxidative stability of milk and expression of oxidative stress response, lipogenic-related, and IGF-1 genes in early-lactation cows supplemented with peanut and sunflower oils

Context Feeding dairy cows with plant oils rich in unsaturated fatty acids is a recommended strategy for increasing the proportion of polyunsaturated fatty acids in milk for human consumption. Aims We evaluated the effects of supplementation with peanut oil (high oleic acid content) and sunflower oil (high linoleic acid content) on the fatty acid profile and oxidative stability of milk and the expression of oxidative stress response, lipogenic-related and insulin-like growth factor 1 (IGF-1) genes in pasture-fed Jersey cows in early lactation. Methods Twenty-four cows were distributed in a randomised block design. Treatments were four dietary supplements of concentrate alone, or concentrate plus oil (59.6 g/kg dry matter): peanut oil, sunflower oil, or a 1:1 (v/v) mixture of peanut and sunflower oils. Analyses were performed at 30 and 60 days in milk. Key results Both peanut oil and mixed oil diets increased the hypocholesterolemic/hypercholesterolemic ratio (P &lt; 0.001) and health-promoting index (P &lt; 0.001) of milk. The sunflower oil diet increased the thrombogenicity index (P = 0.005) and conjugated diene production (P &lt; 0.001). mRNA abundance of fatty acid synthase (P = 0.003), acetyl-CoA carboxylase alpha (P = 0.001), and stearoyl-CoA desaturase (P &lt; 0.001) decreased with the sunflower oil diet. mRNA abundance of superoxide dismutase decreased (P = 0.01) with sunflower oil and mixed oil diets. The control diet tended (P = 0.08) to reduce IGF-1 mRNA abundance. Conclusions and implications Supplementation with peanut oil increases the health-promoting index of milk, whereas supplementation with sunflower oil increases susceptibility to lipid peroxidation. Supplementation with sunflower oil reduces the expression of lipogenic and antioxidant enzyme genes, and supplementation with unsaturated fats may reduce IGF-1 gene expression in early-lactation cows. The relatively small sample size means that more studies are needed.

A Poly(dA:dT) Tract in the IGF1 Gene Is a Genetic Marker for Growth Traits in Pigs.

Insulin-like growth factor 1 (IGF1) is an important regulator of body growth, development, and metabolism. The poly(dA:dT) tract affects the accessibility of transcription factor binding sites to regulate transcription. Therefore, this study assessed the effects of two poly(dA:dT) tracts on the transcriptional activity of porcine IGF1. The luciferase assay results demonstrated that the poly(dA:dT) tract 2 (-264/-255) was a positive regulatory element for IGF1 gene expression, and the activities between the different lengths of the poly(dA:dT) tract 2 were significant (p&lt;0.01). The transcription factor C/EBPα inhibited the transcription of IGF1 by binding to tract 2, and the expression levels between the lengths of tract 2 after C/EBPα binding were also statistically different (p&lt;0.01). Only the alleles 10T and 11T were found in the tract 2 in commercial pig breeds, while the 9T, 10T, and 11T alleles were found in Chinese native pig breeds. The allele frequencies were in Hardy-Weinberg equilibrium in all pig breeds. The genotypes of tract 2 were significantly associated with the growth traits (days to 115 kg and average daily gain) (p&lt;0.05) in commercial pig breeds. Based on these findings, it can be concluded that the tract 2 mutation could be applied as a candidate genetic marker for growth trait selection in pig breeding programs.

Changes in MCP-1, HGF, and IGF-1 expression in endometrial stromal cells, PBMCs, and PFMCs of endometriotic women following 1,25(OH)2D3 treatment.

1,25(OH)2D3 has anti-inflammatory and growth inhibitory effects. Our study explored the effect of 1,25(OH)2D3 treatment on the expression of monocyte chemotactic protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1) by peripheral blood mononuclear cells (PBMCs), peritoneal fluid mononuclear cells (PFMCs), endometrial stromal cells (ESCs), and its effect on the proliferation of PBMCs and PFMCs of patients with endometriosis compared with controls. PBMCs, PFMCs, and ESCs were obtained from 10 endometriosis patients and 10 non-endometriotic individuals. After treating cells with 0.1μM of 1,25(OH)2D3 for 6, 24, and 48 h, the gene and protein expression of mentioned factors were evaluated by real-time PCR and ELISA methods, respectively. 1,25(OH)2D3 treatment significantly reduced the protein expression of MCP-1, HGF, and IGF-1 in PBMCs and PFMCs of endometriotic patients at 48 h (p&lt; 0.05-&lt;0.01). Also, this treatment significantly reduced MCP-1, HGF, and IGF-1 gene and/or protein expression in EESCs and EuESCs at 24 and 48 h (p&lt; 0.05-&lt;0.01). 1,25(OH)2D3 treatment also reduced the proliferation of PBMCs and PFMCs of endometriotic patients compared with controls (p &lt; 0.01). 1,25(OH)2D3 can be considered as a potentially effective agent in the prevention and treatment of endometriosis along with other therapies.

Effect of Omega-3 Drug and Virgin Coconut Oil in Histopathological and Molecular Changes in Liver of Experimentally Obese Pregnant Albino Rats

The study aimed to evaluate the role of omega-3 and coconut oil in the histological changes caused by obesity in the liver of pregnant obese female rats and to evaluate the molecular change by estimating the gene expression of the insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein (IGFBP-1) genes. The study used 50 albino female rats aging (90-110) and weighting (185-200gr). The experiment included two stages. First stage was to induce obesity by adding (45% fat) to the standard diet, except for the control group. In the second stage, female rats were left to mate and were divided into 5 groups (10 for each group) as follows: G1 was the Control group that remained on a standard diet, G2 was fed a high-fat diet only, G3 was orally dosed with Omega-3 (260 g/kg), G4 was orally dosed with coconut oil (200 mg/kg), G5 was orally dosed with both Omega 3 and coconut oil with the same doses. Animals were sacrificed on the 18th day of pregnancy. Histological examination of the G2 liver showed severe steatosis in hepatocytes, cellular swelling, and congestion in the central portal vein; lipid profile results showed a reduction in total Cholesterol, triglycerides, and LDL-C in the blood serum of groups treated with both omega3 and Coconut oil. Liver in the group treated with Omega 3 alone or with coconut oil showed the normal histological features of the liver tissue. The liver of the G4 group, treated with coconut oil, showed slight cloudy degeneration of some hepatocytes with individual necrosis of some of the others and congestion in the portal vein. Groups treated with omega-3 and coconut oil separately or together showed an increase in the gene expression of IGF-1 and IGFBP-1.

Sprint training interacts with body mass to affect hepatic insulin-like growth factor expression in female green anoles (Anolis carolinensis)

Locomotor performance is a key predictor of fitness in many animal species. As such, locomotion integrates the output of a number of morphological, physiological, and molecular levels of organization, yet relatively little is known regarding the major molecular pathways that bolster locomotor performance. One potentially relevant pathway is the insulin and insulin-like signaling (IIS) network, a significant regulator of physiological processes such as reproduction, growth, and metabolism. Two primary hormones of this network, insulin-like growth factor 1 (IGF1) and insulin-like growth factor 2 (IGF2) are important mediators of these processes and, consequently, of life-history strategies. We sprint-trained green anole (Anolis carolinensis) females to test the responsiveness of IGF1 and IGF2 hepatic gene expression to exercise training. We also tested how sprint training would affect glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and eukaryotic elongation factor 2 (EEF2). The former is a crucial enzyme for glycolytic function in a cell, and the latter is necessary for protein synthesis. Resistance exercise forces animals to increase investment of resources towards skeletal muscle growth. Because IGF1 and IGF2 are important hormones for growth, and GAPDH and EEF2 are crucial for proper cellular function, we hypothesized that these four genes would be affected by sprint training. We found that sprint training affects IGF and EEF2 expression, such that larger sprint-trained lizards express hepatic IGF1, IGF2, and EEF2 to a lesser extent than similarly sized untrained lizards. These results demonstrate that the IIS, and pathways connected to it, can react in a size-dependent manner and are implicated in the exercise response in reptiles.

Effects of Rosa damascena on reproductive improvement, metabolic parameters, liver function and insulin-like growth factor-1 gene expression in estradiol valerate induced polycystic ovarian syndrome in Wistar rats

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. MethodsAdult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. ResultsCompared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (p < 0.001). ConclusionRD extract seems to have the potential therapeutic effect of alleviating PCOS complications, and IGF-1 signaling may be involved in the beneficial effects of RD on PCOS.

A Mixture of Valine and Isoleucine Restores the Growth of Protein-Restricted Pigs Likely through Improved Gut Development, Hepatic IGF-1 Pathway, and Plasma Metabolomic Profile.

Valine (Val) alone or in combination with isoleucine (Ile) improves the growth under severe protein restriction; however, the underlying mechanisms remain unknown. In this study, we assessed whether Val/Ile-induced growth in protein-restricted pigs is associated with changes in gut development, hepatic insulin-like growth factor 1 (IGF-1) production, and blood metabolomics. Forty piglets were assigned to five dietary groups: positive control (PC) with standard protein content; low protein (LP) with very low protein content; and LP supplemented with Val (LPV), Ile (LPI), and Val and Ile (LPVI). LPVI reversed the negative effects of VLP diets on growth and gut morphology. Both LPV and LPVI restored the reduced transcript of IGF-1 while decreasing the transcript of insulin-like growth factor binding protein 1 (IGFBP1) in the liver. LPV and LPVI recovered the reduced plasma Val, glycine, and leucine concentrations, which were positively correlated with improved gut morphology and the hepatic IGF-1 gene expression and negatively correlated with hepatic IGFBP1 mRNA abundance. In conclusion, supplementation with a combination of Val and Ile into the VLP diets restored the decreased growth performance of pigs fed with these diets likely through improved gut development, hepatic IGF-1 expression and bioavailability, and plasma metabolomics profile.

CEBP\u03b2 regulation of endogenous IGF-1 in adult sensory neurons can be mobilized to overcome diabetes-induced deficits in bioenergetics and axonal outgrowth

Aberrant insulin-like growth factor 1 (IGF-1) signaling has been proposed as a contributing factor to the development of neurodegenerative disorders including diabetic neuropathy, and delivery of exogenous IGF-1 has been explored as a treatment for Alzheimer’s disease and amyotrophic lateral sclerosis. However, the role of autocrine/paracrine IGF-1 in neuroprotection has not been well established. We therefore used in vitro cell culture systems and animal models of diabetic neuropathy to characterize endogenous IGF-1 in sensory neurons and determine the factors regulating IGF-1 expression and/or affecting neuronal health. Single-cell RNA sequencing (scRNA-Seq) and in situ hybridization analyses revealed high expression of endogenous IGF-1 in non-peptidergic neurons and satellite glial cells (SGCs) of dorsal root ganglia (DRG). Brain cortex and DRG had higher IGF-1 gene expression than sciatic nerve. Bidirectional transport of IGF-1 along sensory nerves was observed. Despite no difference in IGF-1 receptor levels, IGF-1 gene expression was significantly (P < 0.05) reduced in liver and DRG from streptozotocin (STZ)-induced type 1 diabetic rats, Zucker diabetic fatty (ZDF) rats, mice on a high-fat/ high-sugar diet and db/db type 2 diabetic mice. Hyperglycemia suppressed IGF-1 gene expression in cultured DRG neurons and this was reversed by exogenous IGF-1 or the aldose reductase inhibitor sorbinil. Transcription factors, such as NFAT1 and CEBPβ, were also less enriched at the IGF-1 promoter in DRG from diabetic rats vs control rats. CEBPβ overexpression promoted neurite outgrowth and mitochondrial respiration, both of which were blunted by knocking down or blocking IGF-1. Suppression of endogenous IGF-1 in diabetes may contribute to neuropathy and its upregulation at the transcriptional level by CEBPβ can be a promising therapeutic approach.

Gene Therapy - Can it Cure Type 1 Diabetes?

Type 1 diabetes (T1D) is one of the most prevalent early-onset autoimmune diseases, and numerous treatment regimens have been developed over the years with a mainstay focus on insulin injections, infusions, and pumps. However, with the evolution of modern medicine in the recent decade, can gene therapy be a possible solution to prevent and even cure this autoimmune diabetes? In this review, the authors discuss the present-day advancements around the globe where gene therapy is implemented in different techniques to halt and even reverse T1D. The main focus of the final included studies for this review was to regenerate or preserve pancreatic β cells from other cell types in order to optimize insulin secretions in non-obese autoimmune diabetic patients. A literature search was done in various databases such as PubMed, ScienceDirect, and Google Scholar, and a final of eight studies were included. On the whole, the studies reviewed suggested favorable results of gene therapy, although these researches were done mainly in vitro or as animal studies. The application of different virus vector encoding gene transfer through transcription factors, mRNA electroporation, insulin-like growth factor gene expression as well as combination gene transfer concluded beneficial effects on normalizing insulin production, which could pave the path to perfecting gene therapy, and may even find a permanent cure for T1D in the near future.

Effects of folic acid supplementation to basal diets of broilers on growth performance, slaughter performance, IGF2 gene expression and methylation

Folic acid (FA) is an important water-soluble vitamin and plays an important role as a cofactor and coenzyme in animal growth and development, and regulation of gene expression and methylation. A total of 270 female broiler chickens (1-day-old) were randomly allotted to three dietary treatments supplemented with 0 mg/kg (control group), 5 mg/kg, and 10 mg/kg FA in basal diets for 42 days, respectively. Each treatment had six replicate cages with 15 birds per cage. Dietary supplementation of 5 mg/kg FA significantly enhanced average body weight and average daily gain of 21-day-old broilers (P &amp;lt; 0.05), but significantly reduced subcutaneous fat thickness and widths of an intermuscular fat band of 42-day-old broilers by dietary FA treatments (P &amp;lt; 0.05). Also, a diet with 10 mg/kg FA supplementation significantly increased the relative heart weight of 42-day-old chickens (P &amp;lt; 0.05). Furthermore, dietary FA supplementation significantly improved the serum insulin-like growth factor 2 (IGF2) concentrations (P &amp;lt; 0.01) and IGF2 mRNA expression in the abdominal fat (P &amp;lt; 0.05), but no statistical differences were found in the methylation of IGF2 promoter (P &amp;gt; 0.05). The present study demonstrated that dietary FA supplementation may have positive effects on chicken growth through increased IGF2 gene expression.

Expression levels of MCP-1, HGF, and IGF-1 in endometriotic patients compared with non-endometriotic controls

BackgroundTo study the concentrations of monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1) in peritoneal fluid (PF) and serum, and to evaluate their expressions by PF and peripheral blood mononuclear cells (PFMCs and PBMCs, respectively), and ectopic and eutopic endometrial stromal cells of patients with endometriosis (EESCs and EuESCs, respectively) compared with controls.MethodsThe concentrations of mentioned cytokines in serum and PF, as well as their expression in PBMCs, PFMCs, EuESCs and EESCs from endometriosis patients and controls were assessed.ResultsThe levels of MCP-1, HGF, and IGF-1 in serum and PF in women with endometriosis were significantly higher than the controls (P < 0.05–P < 0.001). Gene expression of MCP-1 and IGF-1 in the PFMCs, PBMCs and EESCs also showed an increased level compared to controls (P < 0.05–P < 0.01). The protein expression of MCP-1 and IGF-1 by PFMCs was statistically higher in endometriotic women (P < 0.05 and P < 0.01, respectively). The gene and protein expression of HGF in PFMCs and its gene expression by EESCs were significantly higher in endometriotic women compared to controls (P < 0.05–P < 0.01).ConclusionsThe higher concentrations of mentioned cytokines in serum and PF and their higher expression by PFMCs and EESCs in endometriosis patients may contribute to the development of endometriosis.

Different expression of LHR, PRLR, GH and IGF1 during testicular development of yak

AbstractLuteinizing hormone receptor (LHR), prolactin receptor (PRLR), growth hormone (GH) and insulin‐like growth factor 1 (IGF1) have been shown to be key regulators of germ cell development. However, the role of LHR, PRLR, GH and IGF1 in the development of yak testis remains unclear. In this study, we aimed to describe and compare gene expression and protein localization of LHR, PRLR, GH and IGF1 in the development of yak testes. Testes were collected from 6, 24, 36 and 72 months yak, and the kidney, liver, testicular, lung, skeletal muscle, heart and spleen tissues were collected from 36 months yak. The quantitative real‐time PCR (qRT‐PCR) results showed that the expression of these four genes was widely expressed in kidney, liver, testicular, lung, skeletal muscle, heart and spleen, while the LHR and PRLR were highly expressed in the kidney, skeletal muscle and testis, and higher levels of GH and IGF were expressed in spleen and testis. Moreover, the mRNA expression of these genes in adults was higher than in pre‐pubertal yak. In the testis, the LHR‐, PRLR‐, GH‐ and IGF1‐positive signals were detected in the Leydig cells of the 6 months, while the intense positive signals were discovered in Leydig cells, spermatogonia and spermatocytes of the 36 and 72 months. Thus, LHR, PRLR, GH and IGF1 may be involved in the development of spermatids and spermatocytes, and in the regulation of spermatogonia proliferation and Leydig cell function.