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J. pediatr. (Rio J.) ; 98(1): 76-83, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1360550


Abstract Objective: To determine the prevalence of vitamin A deficiency (VAD) and serum concentrations of retinol, correlating them with IGF-1 concentrations in preschoolers with DS. Methods: Cross-sectional study was conducted on 47 children with DS aged 24 to 72 months, in Ribeirão Preto, Brazil. VAD was determined by the relative dose-response (RDR) test. Retinol serum concentration ≤ 0.70 μmol/L and IGF-1 serum concentration below the 3rd percentile for sex and age were considered to represent deficiency. C-reactive protein (CRP) was determined at the beginning of the study. Weight, height, and information about fever and/or diarrhea were obtained at the beginning of the study. Results: VAD prevalence was 25.5% (12/47), and 74.5% (35/47) of the children had deficient retinol before the intervention. CRP was not associated with VAD. Mean IGF-1 were 103.5 ng/mL (SD = 913) for the group with VAD and 116.3 ng/mL (SD = 54.9) for the group with no VAD (p-value = 0.85); 8.5% (4/47) of the children showed deficient IGF-1, but without VAD. No association was observed between VAD and IGF-1 deficiency. A moderate positive correlation was observed between pre-intervention retinol and IGF-1 (ρ = 0.37; p-value = 0.01). Conclusion: a high prevalence of VAD and deficient retinol was observed and there was a positive correlation between serum retinol and IGF-1.

Humans , Child, Preschool , Child , Vitamin A Deficiency/epidemiology , Insulin-Like Growth Factor I/analysis , Down Syndrome , Vitamin A , Brazil/epidemiology , Prevalence , Cross-Sectional Studies
Article in English | WPRIM | ID: wpr-928586


OBJECTIVES@#To study the serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in children with autism spectrum disorder (ASD) and their association with the core symptoms of ASD.@*METHODS@#A total of 150 ASD children aged 2-7 years (ASD group) and 165 healthy children matched for age and sex (control group) who were recruited at the outpatient service of Chongqing Health Center for Women and Children were enrolled as subjects. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the core symptoms of the ASD children. Chemiluminescence was used to measure the serum levels of IGF-1 and IGFBP-3 in both groups.@*RESULTS@#The ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). The children with severe ASD had significantly lower serum levels of IGF-1 and IGFBP-3 than those with mild-to-moderate ASD (P<0.001). For the children aged 2-3 years, the ASD group had a significantly lower serum level of IGF-1 than the control group (P<0.05). Boys had a significantly lower serum level of IGF-1 than girls in both ASD and control groups (P<0.05). The serum levels of IGF-1 and IGFBP-3 were negatively correlated with the total score of CARS (r=-0.32 and -0.40 respectively, P<0.001).@*CONCLUSIONS@#The reduction in serum IGF-1 level in early childhood may be associated with the development of ASD, and the serum levels of IGF-1 and IGFBP-3 are associated with the core symptoms of ASD children.

Autism Spectrum Disorder , Autistic Disorder , Child , Child, Preschool , Female , Humans , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor I , Male
J. pediatr. (Rio J.) ; 97(6): 595-602, Nov.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350976


Abstract Objective: To discuss the approach to patients diagnosed with growth hormone deficiency (GHD) in childhood during the transition period from puberty to adulthood, focusing on the following: (1) physiology; (2) effects of recombinant human GH (rhGH) interruption/reinstitution after adult height achievement; (3) re-evaluation of somatrotropic axis; (4) management of rhGH reinstitution, when necessary. Source of data: Narrative review of the literature published at PubMed/MEDLINE until September 2020 including original and review articles, systematic reviews and meta-analyses. Synthesis of data: Growth hormone is crucial for the attainment of normal growth and for adequate somatic development, which does not end concomitantly with linear growth. Retesting adolescents who already meet the criteria that predict adult GHD with high specificity is not necessary. Patients with isolated GHD have a high likelihood of normal response to GH testing after puberty. Adolescents with confirmed GHD upon retesting should restart rhGH replacement and be monitored according to IGF-I levels, clinical parameters, and complementary exams. Conclusion: Patients with isolated idiopathic GHD in childhood are a special group who must be reevaluated for GHD as many of them have normal GH provocative tests upon retesting after puberty. Patients who confirm the persistence of GHD in the transition period should maintain rhGH replacement in order to reach an ideal peak bone mass, satisfactory body composition, lipid and glucose profiles, and quality of life.

Humans , Child , Adolescent , Adult , Human Growth Hormone , Transition to Adult Care , Quality of Life , Insulin-Like Growth Factor I , Growth Hormone , Puberty
Arq. bras. med. vet. zootec. (Online) ; 73(5): 1217-1224, Sept.-Oct. 2021. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1345258


This work aimed to assess the effect of the probiotic strain, Lactobacillus plantarum, on the levels of leptin, IGF-1 and their receptors on the hepatopancreatic tissues of Nile tilapia (Oreochromis niloticus) and then correlate fish growth performance and gut microbiological parameters. Fish juveniles (±23g) were reared in a recirculation system with constant aeration and temperature (25°C). They were distributed into six polyethylene tanks (45L) and fed twice a day at 5% of the tank biomass with the respective diets: control (commercial diet without probiotic) and supplemented with L. plantarum inoculum (1 x 108 CFU mL-1), both in triplicate. After 30 days of feeding, L. plantarum-fed fishes showed greater weekly growth rate, final weight, and feed conversion rate, in addition to higher count of lactic-acid bacteria and lower count of pathogenic bacteria in the intestinal tract, when compared to the control group. The immunostaining intensity for IGF-1 and leptin hormones was lower after L. plantarum supplementation than in the control group, with no change in the level for receptors. This reduction could implicate important changes in fish metabolism and homeostasis.(AU)

O presente trabalho teve como objetivo avaliar o efeito da cepa probiótica Lactobacillus plantarum sobre os níveis de leptina, IGF-1 e seus receptores no tecido hepatopancreático de tilápia-do-nilo (Oreochromis niloticus) e correlacionar com o desempenho zootécnico e os parâmetros microbiológicos intestinais dos peixes. Juvenis de tilápia-do-nilo (±23g) foram distribuídos em seis tanques de polietileno (45L) conectados a um sistema de recirculação, com aeração e temperatura constantes (25°C). Os peixes foram alimentados duas vezes ao dia, a 5% da biomassa do tanque, com as respectivas dietas: controle (dieta comercial sem probiótico) e suplementada com L. plantarum (1 x 108 UFC mL-1), ambas em triplicata. Após 30 dias de cultivo, os peixes alimentados com L. plantarum apresentaram maiores ganho de peso semanal, peso final e conversão alimentar, bem como maior contagem de bactérias ácido-láticas e menor contagem de bactérias patogênicas no trato intestinal das tilápias alimentadas com dieta probiótica, em comparação ao grupo controle. A intensidade da imunomarcação para os hormônios IGF-1 e leptina foi menor com a suplementação de L. plantarum do que no grupo controle, sem alterar os níveis de seus receptores. Essa redução pode implicar mudanças importantes no metabolismo e na homeostase dos peixes.(AU)

Animals , Cichlids/growth & development , Hepatopancreas/chemistry , Lactobacillus plantarum , Gastrointestinal Microbiome , Animal Feed , Insulin-Like Growth Factor I , Dietary Supplements , Leptin
Rev. bras. med. esporte ; 27(3): 295-298, July-Sept. 2021. graf
Article in English | LILACS | ID: biblio-1288566


ABSTRACT Introduction Skeletal muscle injuries account for 10% to 50% of treadmill sports injuries. Insulin-like growth factor (IGF) is a family of polypeptides with both insulin-like anabolic and growth-promoting effects. Sports play a vital role in the recovery of skeletal muscle injuries. Objective The paper analyzes the ability of insulin-like growth factor 1 (IGF-1) to repair skeletal muscle injury caused by treadmill exercise. Method We injected drugs under the wound after exercise-induced injury in rats. The control group was injected with saline, and the experimental group was injected with an insulin-like growth factor. We conduct histological and electron microscopic structural analysis of rats, Results: After an injury, the experimental group formed a basal lamina protective film earlier than the control group, activated myoblasts, formed myofilaments, formed myotubes, and fused into muscle fibers earlier than the control group. The healing quality was also better. The experimental group was endogenous. The mRNA content of sex IGF-1 and IGF-2 both increased earlier than the control group. Conclusion Local injection of exogenous insulin-like growth factor-1 can stimulate the proliferation of myoblasts and accelerate the post-traumatic repair process of skeletal muscle caused by treadmill sports. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução As lesões do músculo esquelético representam de 10% a 50% das lesões em esteira esportiva. O fator de crescimento semelhante à insulina (IGF) é uma família de polipeptídeos com efeitos anabólicos e de promoção do crescimento semelhantes à insulina. Os esportes desempenham um papel vital na recuperação de lesões musculares esqueléticas. Objetivo o artigo analisa a capacidade do fator de crescimento semelhante à insulina 1 (IGF-1) em reparar lesões musculares esqueléticas causadas por exercícios em esteira. Método Injetamos drogas sob a ferida após lesão induzida por exercício em ratos. O grupo controle foi injetado com solução salina e o grupo experimental foi injetado com um fator de crescimento semelhante à insulina. Realizamos análises histológicas e microscópicas eletrônicas estruturais de ratos. Resultados Após a lesão, o grupo experimental formou um filme protetor da lâmina basal mais cedo do que o grupo controle, mioblastos ativados, miofilamentos formados, miotubos formados e fundidos em fibras musculares mais cedo do que o grupo controle. A qualidade da cura também foi melhor. O grupo experimental era endógeno. O conteúdo do sexo IGF-1 e IGF-2 mRNA aumentou mais cedo do que no grupo de controle. Conclusão A injeção local de fator de crescimento semelhante à insulina 1 exógeno pode estimular a proliferação de mioblastos e acelerar o processo de reparo muscular esquelético pós-traumático causado por esportes em esteira. Nível de evidência II; Estudos terapêuticos: investigação dos resultados do tratamento.

RESUMEN Introducción Las lesiones del músculo esquelético representan del 10% al 50% de las lesiones deportivas en cinta. El factor de crecimiento semejante a la insulina (IGF) es una familia de polipéptidos con efectos anabólicos y estimulantes del crecimiento semejantes a la insulina. Los deportes juegan un papel vital en la recuperación de las lesiones del músculo esquelético. Objetivo El artículo analiza la capacidad del factor de crecimiento semejante a la insulina 1 (IGF-1) para reparar la lesión del músculo esquelético causada por el ejercicio en cinta. Método inyectamos drogas debajo de la herida después de una lesión inducida por el ejercicio en ratas. Al grupo de control se le inyectó solución salina y al grupo experimental se le inyectó un factor de crecimiento semejante a la insulina. Realizamos análisis estructurales histológicos y microscópicos electrónicos de ratas, Resultados: Después de una lesión, el grupo experimental formó una película protectora de la lámina basal antes que el grupo de control, activó mioblastos, formó miofilamentos, formó miotubos y se fusionó en fibras musculares antes que el grupo de control. La calidad de curación también fue mejor. El grupo experimental fue endógeno. El contenido de ARNm de IGF-1 e IGF-2 de sexo aumentaron antes que en el grupo de control. Conclusión La inyección local de factor de crecimiento semejante a la insulina 1 exógeno puede estimular la proliferación de mioblastos y acelerar el proceso de reparación postraumático del músculo esquelético causado por los deportes en cinta. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Humans , Male , Rats , Wound Healing/drug effects , Insulin-Like Growth Factor I/administration & dosage , Muscle, Skeletal/injuries , Acute Disease , Muscle, Skeletal/drug effects , Muscle, Skeletal/ultrastructure , Disease Models, Animal
Rev. cuba. endocrinol ; 32(2): e232, 2021. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1347401


La aparición de nódulos tiroideos en las personas con acromegalia es una consecuencia de la elevación crónica de la hormona de crecimiento y el factor de crecimiento similar a la insulina tipo 1. Su naturaleza varía según la zona geográfica, suficiencia de yodo y antecedentes patológicos familiares, entre otros factores. No se han publicado estudios cubanos sobre la enfermedad nodular tiroidea en estas personas. Objetivos: Describir las características clínicas, bioquímicas y ultrasonográficas de la glándula tiroidea, según la presencia o no de la enfermedad nodular tiroidea. Métodos: Estudio observacional descriptivo, transversal, que incluyó 73 pacientes con acromegalia entre enero de 2003 y diciembre de 2017. Se estudiaron las variables: edad, sexo, color de la piel, antecedentes familiares de la enfermedad nodular tiroidea, niveles de la hormona de crecimiento, hormona estimulante del tiroides, T4 libre, anticuerpos contra la peroxidasa tiroidea y contra la tiroglobulina, volumen tiroideo, patrón ecográfico nodular y estudio citológico. Resultados: La enfermedad nodular tiroidea se presentó en el 75,3 por ciento de los casos, con predominio del bocio multinodular. La edad al diagnóstico fue menor en los pacientes con la enfermedad (43,53 ± 9,67), que en los que no la tenían (49,33 ± 6,96 años) (p = 0,02). La hormona de crecimiento al diagnóstico de acromegalia, resultó menor en los pacientes con este padecimiento (18,73 ± 11,33 µg/L vs. 35,91 ± 21,68 µg/L; (p = 0,00). El volumen tiroideo mostró diferencias significativas entre ambos grupos (14,2 ± 4,5 mL en los casos positivos de la enfermedad nodular tiroidea y 10,5 ± 2,8 mL en los casos negativos; p = 0,002), siendo el nódulo de baja sospecha de malignidad el más frecuente. El resto de las variables resultaron similares entre los pacientes con y sin la enfermedad. La citología se informó como benigna en el 75 por ciento en los nódulos únicos, el 80 por ciento de los bocios nodulares y el 90 por ciento de los bocios multinodulares (p = 0,51). Conclusiones: La enfermedad nodular tiroidea fue frecuente en los casos de acromegalia, y se asoció a la menor edad y los niveles inferiores de la hormona de crecimiento al diagnóstico. El bocio multinodular constituyó la forma clínica más frecuente y los parámetros hormonales y de autoinmunidad no se asociaron al tipo de la enfermedad nodular tiroidea(AU)

The appearance of thyroid nodules in people with acromegaly is a consequence of chronic elevation of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1). Its nature varies according to the geographical area, the iodine sufficiency and family pathological history, among other factors. No Cuban studies on thyroid nodular disease (TND) in these people have been published. Objectives: Describe some clinical characteristics, as well as biochemical and ultrasonographic ones related to the thyroid gland, according to the presence or not of TND, and to identify the possible association of clinical, biochemical, ultrasonographic and cytological factors with the different types of TND in patients with acromegaly. Methods: A descriptive, cross-sectional observational study that included 73 patients with acromegaly between January 2003 and December 2017. The following variables were studied: age, sex, skin color, family history of TND, GH levels, thyroid stimulating hormone, free T4, antibodies against thyroid peroxidase and thyroglobulin, thyroid volume, nodular ultrasound pattern and cytological study. Results: TND occurred in 75.3 percent of cases, with a predominance of multinodular goiter. The age at diagnosis time was lower in patients with TND (43.53 ± 9.67) than in those who did not have it (49.33 ± 6.96 years) (p=0.02). GH at diagnosis time of acromegaly was lower in patients with TND (18.73±11.33µg/L vs 35.91±21.68µg/L; (p=0.00). The thyroid volume showed significant differences between both groups (14.2±4.5mL in positive cases of TND and 10.5±2.8mL in negative cases; p=0.002), being the most frequent the nodule with low suspicion of malignancy. The rest of the variables were similar between patients with and without TNDs. Cytology was reported as benign in 75 percent in single nodules, 80 percent of nodular goiters and 90 percent of multinodular goiters (p=0.51). Conclusions: TND was frequent in cases of acromegaly, and was associated with lower age and lower GH levels at diagnosis time. Multinodular goiter was the most frequent clinical form and hormonal and autoimmunity parameters were not associated with the type of TND(AU)

Humans , Acromegaly/diagnosis , Insulin-Like Growth Factor I/adverse effects , Thyroid Nodule/diagnostic imaging , Human Growth Hormone , Epidemiology, Descriptive , Cross-Sectional Studies , Observational Studies as Topic
Arq. bras. med. vet. zootec. (Online) ; 73(2): 311-319, Mar.-Apr. 2021. tab
Article in English | LILACS, VETINDEX | ID: biblio-1248952


The objective of this study was to evaluate the rate of conception, metabolic, and structural conditions of cryopreserved bovine sperm cells, plus extender with IGF-1 and glutathione (GSH). 12 ejaculations of Nelore bulls were used, submitted to treatments: control, gSH (2mM/mL), IGF-1 (100ng/mL) and gSH (1mM/mL) + IGF-1 (50ng/mL). After cryopreservation and thawing the semen passed the fast thermo resistance test (TTR), plasma membrane and acrosomal integrity (PIAI), mitochondrial membrane potential (AP), oxidative stress, and conception rate. Tukey test was used for the statistical analysis of the parametric variables and the Friedman test for nonparametric. The gestation percentage was compared by the Chi-square test. There was no statistical difference (P<0.05) between treatments for the TTRr variable. Otherwise in the oxidative stress evaluated with the CellROX probe was noted that the IGF-1 showed the highest number of reactive cells (P<0.05). The PIAI, AP and gestation rate showed no difference among treatments (P>0.05), with an average of conceptions of 36.58%. It is concluded that IGF-1, gSH and their association did not cause changes in sperm motility, mitochondrial potential, plasma and acrosomal membrane integrity. IGF-1 increased oxidative stress, however, there was no difference in the gestation rate among the treatments.(AU)

Objetivou-se avaliar a taxa de concepção, as condições metabólicas e estrutural das células espermáticas bovinas criopreservadas, acrescidas de diluidores com fator de crescimento semelhante à insulina do tipo 1(IGF-1) e glutationa (GSH). Foram utilizados 12 ejaculados de touros da raça Nelore, submetidos aos tratamentos: controle, gSH (2mM/mL), IGF-1 (100ng/mL) e gSH (1mM/mL) + IGF-1 (50ng/mL). Após a criopreservação e descongelação, o sêmen passou pelos testes de termorresistência rápida (TTRr), integridade de membrana plasmática e acrossomal (PIAI), alto potencial mitocondrial (AP), estresse oxidativo e taxa de concepção. Utilizou-se o teste de Tukey para as análises estatísticas das variáveis paramétricas e o teste de Friedman para as não paramétricas, com significância de 5%. A percentagem de gestação foi comparada pelo teste do qui-quadrado. Não hove diferença estatística (P<0,05) entre os tratamentos para a variável TTRr. Já no estresse oxidativo avaliado com a sonda CellROX, observou-se que o IGF-1 apresentou maior quantidade de células reativas (P<0,05), 36,38± 24,10. A PIAI, o AP e a taxa de gestação não apresentaram diferença entre tratamentos (P>0,05), com média de concepções de 36,58%. Conclui-se que o IGF-1, a gSH e a sua associação não causaram mudanças na motilidade espermática, no potencial mitocondrial, na integridade da membrana plasmática e acrossomal. O IGF-1 aumentou o estresse oxidativo, porém sem diferença na taxa de gestação entre os tratamentos.(AU)

Animals , Male , Cattle , Semen Preservation/methods , Semen Preservation/veterinary , Insulin-Like Growth Factor I , Cryopreservation/veterinary , Glutathione , Antioxidants/therapeutic use
Article in Chinese | WPRIM | ID: wpr-879429


OBJECTIVE@#To explore the effects of low-frequency electroacupuncture combined with aerobic exercise on sarocopenia, and the effects of IGF-I /Akt and its downstream signaling pathway-related protein.@*METHODS@#Naturally aging SD rats were used as research objects. Thirty-two 6-month-old male SD rats weighing 400 to 450 g were bred to 12-month-old and randomly divided into 4 groups according to body weight:Control group(YC, only grasp, fix, put back, without other intervention), electroacupuncture group (YA, electroacupuncture intervention), exercise group (YE, exercise intervention) and electroacupuncture+exercise group (YEA, electroacupuncture combined with exercise intervention). SD rats were continuously intervened from 12 months to 18 months of age. At the end of the experiment, the conditions of naturally aging rats in each group were observed:skeletal muscle wet weight / weight ratio;HE staining morphology of soleus muscle under light microscope; qPCR was used to detect the expression level of IGF-I mRNA in skeletal muscle;the expression of AKT, mTOR, p70S6K and p-p70S6K proteins in rat gastrocnemius was determined by Western blot.@*RESULTS@#In 18-month-old rats, the intervention period was 6 months. (1) Compared with YC group, YA group and YEA group significantly increased the wet weight / body weight ratio of gastrocnemius muscle in 18 months old rats. YEA group could significantly increase the wet weight / body weight ratio of soleus muscle compared with YC group YC group and YA group (@*CONCLUSION@#Electroacupuncture combined with aerobic exercise can attenuate sarocopenia in 18-month-old naturally aging rats. The molecular mechanism may be related to the promotion of protein synthesis by activating the IGF-I / Akt pathway.

Aging , Animals , Electroacupuncture , Exercise , Insulin-Like Growth Factor I/genetics , Male , Muscle, Skeletal , Proto-Oncogene Proteins c-akt/genetics , Rats , Rats, Sprague-Dawley
Chinese Journal of Biotechnology ; (12): 1249-1259, 2021.
Article in Chinese | WPRIM | ID: wpr-878628


The aim of this study was to investigate the expression of growth hormone (GH) gene on skeletal muscle cell proliferation of Guizhou cattle. The coding sequence of cattle GH gene was amplified by reverse transcription PCR, cloned into the pUCM-T vector and then used to construct the GH gene overexpression vector pEGFP-N3-GH. The expression of the GH gene in skeletal muscle-related tissues (psoas major and longissimus dorsi) of Guizhou cattle was determined by real-time fluorescent quantitative PCR (RT-qPCR). This was followed by culturing and identification of the bovine primary skeletal muscle cells. Subsequently, we introduced the GH gene overexpression vector into the cells to investigate its effect on the proliferation of bovine skeletal muscle cells and the expression of insulin like growth factor 1 and 2 genes related to skeletal muscle growth and development. RT-qPCR results showed that the expression level of GH gene was higher in the psoas major than in the longissimus dorsi of Guizhou cattle, and the expression level in the psoas major of Guanling cattle and Weining cattle was significantly higher than in the longissimus dorsi (P<0.05). The transfection and proliferation results showed that pEGFP-N3-GH significantly increased the expression of GH, IGF-1, and IGF-2 genes in skeletal muscle cells compared to pEGFP-N3 (PP<0.05), and that overexpression of the GH gene also significantly increased the proliferation rate of skeletal muscle cells at the four periods examined (PP<0.01). Our results suggest that GH gene can promote the proliferation of skeletal muscle cells of Guizhou cattle and exerts a positive regulatory effect. This lays the foundation for further exploring the mechanism by which the GH gene affects the growth and development of Guizhou cattle.

Animals , Cattle , Cell Proliferation , Cloning, Molecular , Growth Hormone/genetics , Insulin-Like Growth Factor I/genetics , Muscle, Skeletal
Acta Physiologica Sinica ; (6): 342-352, 2021.
Article in Chinese | WPRIM | ID: wpr-878262


Insulin-like growth factor-1 (IGF-1) is a peptide with a similar molecular structure to insulin. IGF-1 plays a key role in tissue growth and development, as well as cell metabolism, proliferation, differentiation and apoptosis. Liver is the main source of IGF-1, with the production of IGF-1 up to 75% of the total in the whole body, while the remaining 25% are secreted by skeletal muscles, heart, kidney, spleen and other organs. Target organs of IGF-1 include heart, blood vessels, liver, bone and skeletal muscles. It has been well documented that IGF-1 plays an important role in the prevention and treatment of metabolic diseases. Different types of exercise have different effects on IGF-1 expression with organ differences. In this article, we reviewed the preventive and therapeutic effects of IGF-1 on metabolic diseases and IGF-1-mediated exercise-induced benefits.

Exercise Therapy , Humans , Insulin-Like Growth Factor I , Liver , Metabolic Diseases/therapy , Muscle, Skeletal
J. appl. oral sci ; 29: e20200791, 2021. tab, graf
Article in English | LILACS | ID: biblio-1250185


Abstract Background: IGF-1 may be an important factor in bone remodeling, but its mechanism of action on osteoclasts during orthodontic tooth movement is complex and unclear. Methodology: The closed-coil spring was placed between the left maxillary first molar and upper incisors with a force of 50 g to establish an orthodontic movement model. Eighty SD rats were randomized to receive phosphate buffer saline or 400 ng rhIGF-1 in the lateral buccal mucosa of the left maxillary first molar every two days. Tissue sections were stained for tartrate-resistant acidic phosphatase (TRAP), the number of TRAP-positive cells was estimated and tooth movement measured. Results: The rhIGF-1 group exhibited evidential bone resorption and lacuna appeared on the alveolar bone compared to the control group. Moreover, the number of osteoclasts in compression side of the periodontal ligament in the rhIGF-1 group peaked at day 4 (11.37±0.95 compared to 5.28±0.47 in the control group) after the orthodontic force was applied and was significantly higher than that of the control group (p<0.01). Furthermore, the distance of tooth movement in the rhIGF-1 group was significantly larger than that of the control group from day 4 to day 14 (p<0.01), suggesting that rhIGF-1 accelerated orthodontic tooth movement. Conclusion: Our study has showed that rhIGF-1 could stimulate the formation of osteoclasts in the periodontal ligament, and accelerate bone remodeling and orthodontic tooth movement.

Humans , Animals , Rats , Osteoclasts , Tooth Movement Techniques , Periodontal Ligament , Insulin-Like Growth Factor I , Bone Remodeling , Rats, Sprague-Dawley
Arq. bras. med. vet. zootec. (Online) ; 72(3): 664-672, May-June, 2020. tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1128613


Objetivou-se avaliar a condição metabólica e estrutural das células espermáticas bovinas após congelação, com adição prévia de IGF-I e insulina no meio diluidor seminal. Os ejaculados de seis touros Nelore foram submetidos a quatro tratamentos: controle; insulina (100µUI/mL); IGF-I (150ng/mL) e insulina + IGF-I (50µUI/mL e 75ng/mL, respectivamente). Após a congelação, realizaram-se os testes de termorresistência rápida, coloração pelo corante azul de tripan e Giemsa, além da análise computadorizada da motilidade espermática, da integridade das membranas plasmática e acrossomal, e da peça intermediária por meio de sondas fluorescentes. O teste de termorresistência rápida apresentou efeito dentro do tempo de cada tratamento, mas não entre os tratamentos. Na análise computadorizada da motilidade espermática, foram observados movimento, motilidade e velocidade espermáticos; não houve efeitos dos tratamentos sobre qualquer uma dessas variáveis. Respostas iguais foram obtidas com as sondas fluorescentes e o corante azul de tripan/Giemsa. A adição de insulina e IGF-I, de forma isolada ou combinada, ao meio diluidor para congelação de sêmen não produziu efeitos sobre as condições metabólica e estrutural das células espermáticas.(AU)

This study aimed to evaluate the metabolic and structural condition of the spermatic bovine cells after the freezing, with addition, previously, of IGF-I and Insulin in the seminal thinner medium. The semen of 6 Nellore bulls were submitted to four treatments: Control, Insulin (100µUI/mL); IGF-I (150ng/mL) and Insulin + IGF-I (50µUI/mL and 75ng/mL, respectively). After freezing, rapid resistance tests, Tripan and Giemsa Blue staining, and computerized analysis of sperm motility and integrity of the plasma and acrosomal membranes and the intermediate part were performed by fluorescent probes. The term rapid resistance test had effect within the time of each treatment, but not between treatments. In the computer analysis of sperm motility, sperm movement, motility and velocity no effects of treatments were observed on any of these variables. The same results were obtained with the fluorescent probes and the Blue dye Trypan / Giemsa. The addition of Insulin and IGF-I, alone or in combination, to the semen freezing dilution medium had no effect on the metabolic and structural condition of sperm cells.(AU)

Semen/metabolism , Insulin-Like Growth Factor I/administration & dosage , Cryopreservation/veterinary , Insulin/administration & dosage , Cattle , Indicators and Reagents
Arq. bras. med. vet. zootec. (Online) ; 72(2): 523-534, Mar./Apr. 2020. ilus, graf
Article in English | LILACS, VETINDEX | ID: biblio-1128390


Insulin-like growth factor-1 (IGF-1) is regarded as a crucial clinically significant therapeutic agent against several pathological conditions. Recently, recombinant DNA (rDNA) technology has enabled the production of many drugs of rDNA-origin including IGF-1. Securing a readily available supply of IGF-1 is invaluable to clinical research and biotechnological domains. In this work, the cloning of a full-length bovine IGF-1 cDNA and the successful expression of its cognate recombinant IGF-1 protein is reported. Single-strand cDNA was prepared from liver tissues, through the specific reverse transcription (RT) of IGF-1 mRNA. Subsequently, a PCR amplicon of ~543bp was successfully amplified. Recombinant pTARGET™ vector harboring IGF-1 insert was successfully cloned into competent E. coli JM109 cells. SDS-PAGE analysis revealed that the recombinant IGF-1 has been expressed at the expected size of 7.6kDa. The outcome provides a robust basis for transecting the recombinant pTARGETTM vector, harboring the IGF-1 cDNA insert, into mammalian cells. Optimal initial glucose concentration was found to be 10g/l with corresponding protein concentration of 6.2g/l. The proliferative biological activity crude recombinant IGF-1 protein was verified on HeLa cell lines. This is envisaged to facilitate large-scale production of recombinant IGF-1 protein, thereby enabling thorough investigation of its clinical and pharmaceutical effects.(AU)

O fator de crescimento semelhante à insulina-1 (IGF-1) é considerado um agente terapêutico clinicamente significativo contra várias condições patológicas. Recentemente, a tecnologia de DNA recombinante (rDNA) permitiu a produção de muitos medicamentos de origem rDNA, incluindo o IGF-1. Garantir um suprimento prontamente disponível de IGF-1 é inestimável para pesquisas clínicas e domínios biotecnológicos. Neste trabalho, relata-se a clonagem de um cDNA de IGF-1 bovino de comprimento total e a expressão bem-sucedida de sua proteína IGF-1 recombinante cognata. O cDNA de cadeia simples foi preparado a partir de tecidos do fígado, por meio da transcrição reversa específica (RT) do mRNA de IGF-1. Posteriormente, um amplificador de PCR de ~ 543pb foi amplificado com sucesso. O vetor pTARGET™ recombinante contendo a inserção de IGF-1 foi clonado com sucesso em células competentes E. coli JM109. A análise por SDS-PAGE revelou que o IGF-1 recombinante foi expresso no tamanho esperado de 7,6kDa. O resultado fornece uma base robusta para a transferência do vetor pTARGETTMTM recombinante, abrigando a inserção de cDNA de IGF-1 em células de mamíferos. Verificou-se que a concentração inicial ideal de glicose é 10g/L, com a concentração de proteína correspondente de 6,2g/L. A proteína IGF-1 recombinante bruta de atividade biológica proliferativa foi verificada nas linhas celulares HeLa. É previsto que isso facilite a produção da proteína IGF-1 recombinante em larga escala, permitindo, assim, uma investigação completa dos seus efeitos clínicos e farmacêuticos.(AU)

Animals , Recombinant Proteins , Insulin-Like Growth Factor I/genetics , Buffaloes/genetics , Cloning, Molecular , DNA, Complementary , Escherichia coli , Real-Time Polymerase Chain Reaction/veterinary
Arch. endocrinol. metab. (Online) ; 64(1): 82-88, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1088767


ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8

Humans , Male , Female , Adult , Middle Aged , Insulin-Like Growth Factor I/analysis , Hydrocortisone/blood , Human Growth Hormone/blood , Glucose Tolerance Test/methods , Hypoglycemia/blood , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Pituitary-Adrenal System/metabolism , Blood Glucose Self-Monitoring , Retrospective Studies , Glucose Tolerance Test/adverse effects , Hypoglycemia/diagnosis , Hypoglycemia/metabolism , Hypothalamo-Hypophyseal System/metabolism
J. appl. oral sci ; 28: e20190409, 2020. graf
Article in English | LILACS, BBO | ID: biblio-1090768


Abstract Menopause induces oral bone loss, leading to various oral diseases. Mastication importantly affects bone metabolism in the jawbone. Objective: To analyze the effect of enhanced masticatory force on osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), and mechano-growth factor (MGF) in alveolar bone of ovariectomized rats and to study the mechanics mechanism of the alveolar bone of ovariectomized rats response to enhanced masticatory force. Methodology: Thirty Sprague Dawley rats were randomly divided into three groups: sham-operation group (fat around the removed ovary + normal hard diet), model group (ovariectomy + normal hard diet), and experimental group (ovariectomy + high hard diet). It was a 2-month experiment. Enzyme-linked immunosorbent assay (ELISA) detected serum estradiol (E2), osteocalcin (BGP) and alkaline phosphatase (ALP) in rats. Bone histomorphometric indices in the third molar region of maxilla were detected by micro-CT; protein expressions of OPG, RANKL, and MGF in the third molar region of maxilla was detected by Western blot; and gene expression of OPG, RANKL, and MGF in the third molar region of maxilla was detected by Quantitative Real-Time PCR. Results: Comparing with model group, serum E2 in experimental group increased but not significantly, serum BGP and serum ALP in experimental group decreased but not significantly, OPG in experimental group in alveolar bone increased significantly, RANKL in experimental group in alveolar bone decreased significantly, RANKL/OPG ratio in experimental group decreased significantly, MGF in experimental group in alveolar bone increased significantly, bone volume to total volume fraction increased significantly in experimental group, trabecular thickness increased significantly in experimental group, and trabecular separation decreased significantly in experimental group. Conclusion: Enhanced masticatory force affected the expression of OPG, RANKL, and MGF in alveolar bone of ovariectomized rats, improved the quality of jaw bone of ovariectomized rats, and delayed oral bone loss by ovariectomy.

Animals , Female , Bite Force , Insulin-Like Growth Factor I/analysis , Ovariectomy , RANK Ligand/analysis , Osteoprotegerin/analysis , Alveolar Process/physiopathology , Osteocalcin/blood , Blotting, Western , Polymerase Chain Reaction , Rats, Sprague-Dawley , Alkaline Phosphatase/blood , Estradiol/blood , X-Ray Microtomography , Enzyme-Linked Immunospot Assay
Article in English | WPRIM | ID: wpr-816615


BACKGROUND: Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.METHODS: The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.RESULTS: In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.CONCLUSION: The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.

Acromegaly , Blotting, Western , Culture Media , Cyclic AMP , Dopamine Agonists , Dopamine , Enzyme-Linked Immunosorbent Assay , Growth Hormone , Growth Hormone-Secreting Pituitary Adenoma , Humans , In Vitro Techniques , Insulin-Like Growth Factor I , Magnetic Resonance Imaging , Models, Animal , Phosphorylation , Phosphotransferases , Pituitary Neoplasms , Rare Diseases , Receptors, Dopamine , Receptors, Somatostatin , Response Elements , Somatostatin
Arch. endocrinol. metab. (Online) ; 63(6): 608-617, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055027


ABSTRACT The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key components of the somatotropic axis. This axis has been studied for a long time and the knowledge of how some molecules could promote or impair hormones production and action has been growing over the last decade. The enhancement of large-scale sequencing techniques has expanded the spectrum of known genes and several other candidate genes that could affect the GH-IGF1-bone pathway. To date, defects in more than forty genes were associated with an impairment of the somatotropic axis. These defects can affect from the secretion of GH to the bioavailability and action of IGF-1. Affected patients present a large heterogeneous group of conditions associated with growth retardation. In this review, we focus on the description of the GH-IGF axis genetic defects reported in the last decade. Arch Endocrinol Metab. 2019;63(6):608-17

Humans , Insulin-Like Growth Factor I/genetics , Human Growth Hormone/deficiency , Human Growth Hormone/genetics , Growth Disorders/genetics , Mutation/genetics , Phenotype , Insulin-Like Growth Factor I/metabolism , Signal Transduction , Genotype , Growth Disorders/metabolism
Arch. endocrinol. metab. (Online) ; 63(6): 618-629, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055014


ABSTRACT In addition to auxiological, clinical and metabolic features measurements of growth hormone (GH) and insulin-like growth factor I (IGF-I) complement our tools in diagnosis and follow-up of GH-related disorders. While comparably robust during the pre-analytical phase, measurement and interpretation of concentrations of both hormones can be challenging due to analytical issues and biological confounders. Assay methods differ in terms of antibody specificity, interference from binding proteins, reference preparations and sensitivity. GH assays have different specificity towards different GH-isoforms (e.g. 20 kDa GH, placental GH) and interference from the GH antagonist Pegvisomant. The efficacy to prevent binding protein interference is most important in IGF-I assays. Methodological differences between assays require that reference intervals and diagnostic cut-offs are assay-specific. Among biological variables, pubertal development and age are most relevant for IGF-I, making detailed reference intervals mandatory for interpretation. GH has pulsatile secretion and short half-life. Its concentration is modified by acute factors such as stress, exercise and sleep, but also by intake of oral estrogens and anthropometric factors (e.g. BMI). Other GH dependent biomarkers such as free IGF-I, IGF binding protein 3 (IGFBP 3) and acid labile subunit (ALS) have been proposed. Their concentrations largely mirror the information obtained through measurement of IGF-I, but their measurement can be helpful in particular situations. In this review, we describe the evolution of analytical methods to measure biomarkers of GH action, the impact of the methodological changes on laboratory results and the need to include biological variables in their interpretation. Arch Endocrinol Metab. 2019;63(6):618-29

Humans , Insulin-Like Growth Factor I/analysis , Human Growth Hormone/blood , Growth Disorders/diagnosis , Reference Values , Biomarkers/blood , Follow-Up Studies , Sensitivity and Specificity