Insulin Like Growth Factor
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PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260887
Wei-Hung Chan ◽  
Nian-Cih Huang ◽  
Yi-Wen Lin ◽  
Feng-Yen Lin ◽  
Chien-Sung Tsai ◽  

Previous studies have shown an increase of insulin-like growth factor-2 (IGF2) in animal models of neuropathic pain. We aimed to examine the hypothesis that reducing the expression of IGF2 using intrathecal IGF2 small-interfering RNA (siRNA) would attenuate the development of neuropathic pain in rats after spared nerve injury (SNI). Male Wistar rats were divided into three groups: sham-operated group, in which surgery was performed to cut the muscles without injuring the nerves; SNI group, in which SNI surgery was performed to sever the nerves; and SNI + siRNA IGF2 group, in which SNI surgery was performed, and IGF2-siRNA was administered intrathecally 1 day after SNI. The rats were assessed for mechanical allodynia and cold allodynia 1 day before surgery (baseline), and at 2, 4, 6, 8, and 10 days after siRNA treatment. The rat spinal cord was collected for quantitative polymerase chain reaction and western blot analysis. Compared with the SNI group, rats that received IGF2 siRNA showed a significantly increased SNI-induced paw-withdrawal threshold to metal filament stimulation from Day 4 to Day 10 after SNI surgery. IGF2 siRNA significantly decreased the response duration from the acetone test from Day 2 to Day 10 following SNI surgery. SNI increased IGF2 mRNA expression on Day 2 and increased IGF2 protein expression on Day 8 and Day 10 in the spinal cord of the SNI rats. However, the above-mentioned effects of IGF2 mRNA and protein expression were significantly inhibited in the SNI + IGF2 siRNA group. We demonstrated that intrathecal administration of IGF2 siRNA provided significant inhibition of SNI-induced neuropathic pain via inhibition of IGF2 expression in the spinal cord. The analgesic effect lasted for 10 days. Further exploration of intrathecal IGF2 siRNA administration as a potential therapeutic strategy for neuropathic pain is warranted.

Patricia Snarski ◽  
Sergiy Sukhanov ◽  
Tadashi Yoshida ◽  
Yusuke Higashi ◽  
Svitlana Danchuk ◽  

Objective: IGF-1 (insulin-like growth factor 1) exerts pleiotropic effects including promotion of cellular growth, differentiation, survival, and anabolism. We have shown that systemic IGF-1 administration reduced atherosclerosis in Apoe −/ − (apolipoprotein E deficient) mice, and this effect was associated with a reduction in lesional macrophages and a decreased number of foam cells in the plaque. Almost all cell types secrete IGF-1, but the effect of macrophage-derived IGF-1 on the pathogenesis of atherosclerosis is poorly understood. We hypothesized that macrophage-derived IGF-1 will reduce atherosclerosis. Approach and Results: We created macrophage-specific IGF-1 overexpressing mice on an Apoe − / − background. Macrophage-specific IGF-1 overexpression reduced plaque macrophages, foam cells, and atherosclerotic burden and promoted features of stable atherosclerotic plaque. Macrophage-specific IGF1 mice had a reduction in monocyte infiltration into plaque, decreased expression of CXCL12 (CXC chemokine ligand 12), and upregulation of ABCA1 (ATP-binding cassette transporter 1), a cholesterol efflux regulator, in atherosclerotic plaque and in peritoneal macrophages. IGF-1 prevented oxidized lipid-induced CXCL12 upregulation and foam cell formation in cultured THP-1 macrophages and increased lipid efflux. We also found an increase in cholesterol efflux in macrophage-specific IGF1–derived peritoneal macrophages. Conclusions: Macrophage IGF-1 overexpression reduced atherosclerotic burden and increased features of plaque stability, likely via a reduction in CXCL12-mediated monocyte recruitment and an increase in ABCA1-dependent macrophage lipid efflux.

Jayati Joshipura ◽  
Vani H.N. ◽  
Nabanita Kora

Tumour-induced hypoglycaemia is a rare complication/condition mainly seen in adults. It is caused due to increased production of insulin or insulin-like growth factor (IGF) 2 tumour cells. We present a 3-year-old paediatric patient with non-islet cell tumour induced hypoglycaemia (NICTH) secondary to rhabdomyosarcoma. She presented with abdominal mass and refractory hypoglycaemia, requiring high glucose infusion and steroids. Critical sample analysis during hypoglycaemia showed suppression of insulin, IGF-1, C-peptide, growth hormone, and ketones, with a high cortisol level. CT scan of abdomen and pelvis showed a huge retroperitoneal mass, later diagnosed as rhabdomyosarcoma. In a resource-limited setting, where IGF-2 is not possible, low serum insulin and IGF-1 levels during hypoglycaemia aids in diagnosis of NICTH. This is one of the first few reported paediatric cases with NICTH from India, and we believe that reporting this case would add more information to the existing literature. Thus, NICTH should be suspected in all malignancies presenting with intractable hypoglycaemia irrespective of their age.

Xiuling Li ◽  
Yujie Zhang ◽  
Wenqian Jing ◽  
Weiqi Tang ◽  
Jinyi Xing ◽  

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 < 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 < 0.05). Also, a diet with 10 mg/kg FA supplementation significantly increased the relative heart weight of 42-day-old chickens (P < 0.05). Furthermore, dietary FA supplementation significantly improved the serum insulin-like growth factor 2 (IGF2) concentrations (P < 0.01) and IGF2 mRNA expression in the abdominal fat (P < 0.05), but no statistical differences were found in the methylation of IGF2 promoter (P > 0.05). The present study demonstrated that dietary FA supplementation may have positive effects on chicken growth through increased IGF2 gene expression.  

2021 ◽  
Vol 12 ◽  
Florence Scheffler ◽  
Albane Vandecandelaere ◽  
Marion Soyez ◽  
Dorian Bosquet ◽  
Elodie Lefranc ◽  

IntroductionOocyte quality contributes to the development of an optimal embryo and thus a successful pregnancy. The objective of this study was to analyse the association between oocyte cohort quality and the follicular levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), 25-hydroxy vitamin D (25OHD), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and antithyroid antibodies, as a function of intracytoplasmic sperm injection (ICSI) outcomes.Material and methodsWe conducted a prospective comparative pilot study from January 2013 to December 2017. 59 ICSI cycles constituted an abnormal oocyte cohort (n=34 cycles, in which more than 50% of oocytes presented at least one morphological abnormality) and a normal oocyte cohort (n=25 cycles, in which 50% or less of the oocytes presented at least one morphological abnormality). GH, IGF1, 25OHD, TSH, fT3, fT4 and antithyroid antibodies were measured in follicular fluid.ResultsThe fertilisation rate was lower in the abnormal oocyte cohort (65.5% vs. 80%, respectively, p=0.012). Oocytes’ proportion with at least one abnormality was 79.4% in the abnormal oocyte cohort and 29.0% in the normal oocyte cohort. The mean number of morphological abnormalities per oocyte was significantly higher in the abnormal oocyte cohort. The follicular levels of GH (4.98 vs. 2.75 mIU/L, respectively; p <0.01) and IGF1 (72.1 vs. 54.2 ng/mL, respectively; p=0.05) were higher in the normal oocyte cohort. There was no association with follicular levels of TSH, fT3, fT4, antithyroid antibodies, or 25OHD.ConclusionOocyte cohort quality appears to be associated with follicular levels of GH and IGF1.

2021 ◽  
Natalie Jayne Haywood ◽  
Katherine Bridge ◽  
Cheukyau Luk ◽  
Nele Warmke ◽  
Katie Simmons ◽  

There are at least two distinct types of thermogenic adipocyte in mammals: a pre-existing form established during development, termed classical brown adipocytes and an inducible form, beige adipocytes. Various environmental cues can stimulate a process frequently referred to as beiging of white adipose tissue (WAT), leading to enhanced thermogenesis and obesity resistance. Whilst beiging of WAT as a therapeutic goal for obesity and obesity-related complications has attracted much attention; therapeutics stimulating beiging without deleterious side-effects remain elusive10. The endothelium lines all blood vessels and is therefore in close proximity to all cells. Many studies support the possibility that the endothelium acts as a paracrine organ. We explored the potential role of endothelial insulin-like growth factor-1 receptor (IGF-1R) as a paracrine modulator of WAT phenotype. Here we show that a reduction in endothelial IGF-1R expression in the presence of nutrient excess leads to white adipocyte beiging, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell autonomous paracrine mechanism. We demonstrate that this is mediated by endothelial release of malonic acid, which we show, using prodrug analogues, has potentially therapeutically-relevant properties in the treatment of metabolic disease.

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4333
Wojciech Strojny ◽  
Wojciech Czogała ◽  
Przemysław Tomasik ◽  
Mirosław Bik-Multanowski ◽  
Małgorzata Wójcik ◽  

Insulin-like growth factors (IGF-1 and IGF-2) and insulin-like growth factor-binding proteins (IGFBP-1 to -7) are involved in the regulation of cell proliferation and differentiation and may be associated with various metabolic parameters. The aim of our study was to compare levels of IGFs and IGFBPs and the expressions of their genes in children before and after hematopoietic stem cell transplantation (HSCT) to assess their potential as markers of late metabolic complications of HSCT. We also conducted additional comparisons with healthy controls and of correlations of IGF and IGFBP levels with anthropometric and biochemical parameters. We analyzed 19 children treated with HSCT and 21 healthy controls. We found no significant differences in the levels of IGFs and IGFBPs and expressions of their genes before and after HSCT, while IGF and IGFBP levels were significantly lower in children treated with HSCT compared with controls. We conclude that our results did not reveal significant differences between the levels of IGFs and IGFBPs before and after HSCT, which would make them obvious candidates for markers of late complications of the procedure in children. However, due to the very low number of patients this conclusion must be taken with caution and may be altered by further research.

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4191
Nesrein M. Hashem ◽  
Nourhan S. Hosny ◽  
Nagwa I. El-Desoky ◽  
Mohamed G. Shehata

A synbiotic comprising Saccharomyces cerevisiae yeast (SCY) and Moringa oleifera leaf extract (MOLE) has been encapsulated using nanotechnology. This duo is used as a dietary supplement for growing rabbits. Physicochemical analyses, in vitro antimicrobial activity, and gastrointestinal system evaluation were used to evaluate the quality of the nanofabricated synbiotic. The in vivo study was conducted using 40-day-old male growing rabbits (n = 16 rabbits/group) to evaluate the effect of the nanofabricated synbiotic on the health and growth performance of examined rabbits. Rabbits were equally allocated into four groups; (a) NCS, which received a basal diet supplemented with a noncapsulated 11 × 1012 CFU SCY + 0.15 g MOLE/kg diet, (b) LCS: those receiving a nanoencapsulated 5.5 × 1012 CFU SCY + 0.075 g MOLE/kg diet, (c) HCS: those receiving an 11 × 1012 CFU SCY + 0.15 g MOLE/kg diet, and (d) CON: those receiving a basal diet without treatment (control). The treatments continued from day 40 to day 89 of age. During the experimental period, growth performance variables, including body weight (BW), feed consumption, BW gain, and feed conversion ratio were recorded weekly. Blood samples were collected on day 40 of age and immediately before the start of the treatments to confirm the homogeneity of rabbits among groups. On day 89 of age, blood samples, intestinal, and cecal samples were individually collected from eight randomly selected rabbits. The size and polydispersity index of the nanofabricated synbiotic were 51.38 nm and 0.177, respectively. Results revealed that the encapsulation process significantly improved yeast survival through the gastrointestinal tract, specifically in stomach acidic conditions, and significantly increased in vitro inhibitory activities against tested pathogens. Furthermore, treatments had no negative effects on hematobiochemical variables but significantly improved levels of blood plasma, total protein, and insulin-like growth factor-l. Compared to the CON, NCS, and LCS treatments, the HCS treatment increased the amount of intestinal and cecal yeast cells (p < 0.05) and Lactobacillus bacteria (p < 0.05) and decreased number of Salmonella (p < 0.05) and Coliform (p = 0.08) bacteria. Likewise, both LCS and HCS significantly improved the small intestine and cecum lengths compared to CON and NCS. The HCS treatment also significantly improved BW gain and feed conversion compared to CON treatment, whereas the NCS and LCS treatments showed intermediate values. Conclusively, the nanoencapsulation process improved the biological efficiency of the innovative synbiotic used in this study. A high dose of encapsulated synbiotic balanced the gut microflora, resulting in the growth of rabbits during the fattening period.

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3371
Evgenia Gurevich ◽  
Yael Segev ◽  
Daniel Landau

Growth hormone (GH) exerts multiple effects on different organs including the kidneys, either directly or via its main mediator, insulin-like-growth factor-1 (IGF-1). The GH/IGF1 system plays a key role in normal kidney development, glomerular hemodynamic regulation, as well as tubular water, sodium, phosphate, and calcium handling. Transgenic animal models demonstrated that GH excess (and not IGF1) may lead to hyperfiltration, albuminuria, and glomerulosclerosis. GH and IGF-1 play a significant role in the early development of diabetic nephropathy, as well as in compensatory kidney hypertrophy after unilateral nephrectomy. Chronic kidney disease (CKD) and its complications in children are associated with alterations in the GH/IGF1 axis, including growth retardation, related to a GH-resistant state, attributed to impaired kidney postreceptor GH-signaling and chronic inflammation. This may explain the safety of prolonged rhGH-treatment of short stature in CKD.

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1785
Michela L. Mitchell ◽  
Mohammed Akhter Hossain ◽  
Feng Lin ◽  
Ernesto L. Pinheiro-Junior ◽  
Steve Peigneur ◽  

The role of insulin and insulin-like peptides (ILPs) in vertebrate animals is well studied. Numerous ILPs are also found in invertebrates, although there is uncertainty as to the function and role of many of these peptides. We have identified transcripts with similarity to the insulin family in the tentacle transcriptomes of the sea anemone Oulactis sp. (Actiniaria: Actiniidae). The translated transcripts showed that these insulin-like peptides have highly conserved A- and B-chains among individuals of this species, as well as other Anthozoa. An Oulactis sp. ILP sequence (IlO1_i1) was synthesized using Fmoc solid-phase peptide synthesis of the individual chains, followed by regioselective disulfide bond formation of the intra-A and two interchain disulfide bonds. Bioactivity studies of IlO1_i1 were conducted on human insulin and insulin-like growth factor receptors, and on voltage-gated potassium, sodium, and calcium channels. IlO1_i1 did not bind to the insulin or insulin-like growth factor receptors, but showed weak activity against KV1.2, 1.3, 3.1, and 11.1 (hERG) channels, as well as NaV1.4 channels. Further functional studies are required to determine the role of this peptide in the sea anemone.

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