Background: Hyperinsulinemia due to insulin resistance is hypothesized to act as a promotor of cancer growth. In addition to the direct effects of hyperinsulinemia on cancer cells, the stimulation of tumor cell growth can also be indirectly mediated through growth factors and receptors such as insulin-like growth factor 1 (IGF-1). Increased cancer risk is also associated with increased adipose tissue, such as in abdominal obesity, due to the higher risk of insulin resistance and hyperinsulinemia. Waist circumference is a parameter that indicates an individual's level of adiposity. In addition, the risk of cancer also increases in the elderly as they age. This study aims to assess the correlation between waist circumference and IGF-1 levels in the elderly population in Bali, Indonesia. Methodology: This study used a cross-sectional analytical design conducted in the Melinggih Village, Gianyar Regency. The study was conducted in September 2023. This study has been approved by the Research Ethics Commission number 2020/UN14.2.2.VII.14/LT/2023. The study population included elderly individuals residing in the Melinggih Village who were willing to participate. Data analysis encompassed descriptive analysis and the Spearman correlation test. Result: A total of 88 subjects participated in the study, consisting of 57 females (64.8%) and 31 males (35.2%). A statistically significant but weak correlation coexists between waist circumference and IGF-1 levels. Conclusion A weak but statistically significant positive correlation was found between waist circumference and IGF-1 levels in the elderly. However, because of the small sample size, another study with a bigger sample size with enough power to investigate this association needs to be done to validate the results of the current study.
Elderly ; Aged ; IGF-1 ; Insulin-Like Growth Factor I ; Waist Circumference

Background: Growth hormone has been used as an adjunct in ovarian stimulation of IVF cycles for the past three decades. However, the exact mechanism of its role in improving oocyte quality has not been thoroughly investigated. Although a clear indication for GH co-treatment is in infertile women with GH deficiency, GH has been given mostly to poor ovarian responders. Method: This paper is a review of the most recent published data on the role of GH supplementation in improving oocyte quality in younger women who are suboptimal or unexpected poor responders to standard ovarian stimulation. Results: Retrospective cohort and randomized trials demonstrated an improvement in oocyte quality through morphological parameters, mitochondrial function, biomarkers, GH receptors, insulin growth factor, markers of oxidative stress, mature oocytes, good quality embryos, implantation rate, clinical pregnancy and live birth. Conclusion Current data suggest GH supplementation may improve oocyte and embryo qualities, endometrial receptivity, clinical pregnancy and live birth. However, better quality evidence is needed before a recommendation can be made for GH supplementation to be given to infertile women who are suboptimal or poor ovarian responders.
growth hormone ; hormone receptor ; IGF-1 ; IVF

OBJECTIVE: To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells. METHODS: The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation. RESULTS: The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05). CONCLUSION Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.
Animals ; Cell Line, Tumor ; Flavonols/pharmacology* ; Humans ; Mice ; MicroRNAs/metabolism* ; Receptor, IGF Type 1 ; Trastuzumab

OBJECTIVE: To investigate the effect of low-frequency pulsed electromagnetic fields (PEMF) on the maturation and mineralization of rat cranial osteoblasts and its relation to IGF-1R/NO signaling pathway. METHODS: The rat osteoblasts were isolated and cultured and randomly divided into blank control group, PEMF group, GSK group (IGF-1R blocker) and PEMF+GSK group. The cells were treated with 50 Hz 0.6 mT PEMF for 1.5 h/d. After 3 d of PEMF treatment, the expressions of protein kinase (AKT), inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinase (PKG) were detected by Western blotting; on 6 d of PEMF treatment alkaline phosphatase (ALP) activity was determined; on 12 d of PEMF treatment the calcification nodule formation was demonstrated by Alizarin red staining. RESULTS: NO level was significantly increased in rat osteoblasts treated with 50 Hz 0.6 mT PEMF for 1.5 h/d. Western blot analysis showed that the expressions of AKT, iNOS and PKG protein in PEMF group were higher than those in the control group (all <0.01); the ALP activity was increased(<0.05), and the PEMF group had the largest area of Alizarin red staining (<0.01). The expressions of AKT, iNOS and PKG protein in GSK group were lower than those in the control group; the ALP activity was decreased (<0.05), and the GSK group had the least area of Alizarin red staining (<0.01). The expressions of AKT, iNOS, PKG protein, the ALP activity and the area of Alizarin red staining in PEMF+GSK group were between PEMF group and GSK group. CONCLUSIONS PEMF may enhance the maturation and mineralization of rat cranial osteoblasts through IGF-1R/NO signaling pathway.
Animals ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Electromagnetic Fields ; Nitric Oxide ; metabolism ; Osteoblasts ; radiation effects ; Rats ; Receptor, IGF Type 1 ; metabolism ; Signal Transduction ; radiation effects

Insulin-like growth factor-1 receptor (IGF-1R) is involved in both glucose and bone metabolism. IGF-1R signaling regulates the canonical Wnt/β-catenin signaling pathway. In this study, we investigated whether the IGF-1R/ β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis (DOP). Serum from patients with or without DOP was collected to measure the IGF-1R level using enzyme-linked immunosorbent assay (ELISA). Rats were given streptozotocin following a four-week high-fat diet induction (DOP group), or received vehicle after the same period of a normal diet (control group). Dual energy X-ray absorption, a biomechanics test, and hematoxylin-eosin (HE) staining were performed to evaluate bone mass, bone strength, and histomorphology, respectively, in vertebrae. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to measure the total and phosphorylation levels of IGF-1R, glycogen synthase kinase-3β (GSK-3β), and β-catenin. The serum IGF-1R level was much higher in patients with DOP than in controls. DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group. HE staining showed that the histomorphology of DOP vertebrae was seriously impaired, which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae. PCR analysis demonstrated that IGF-1R mRNA expression was significantly up-regulated, and western blotting detection showed that phosphorylation levels of IGF-1R, GSK-3β, and β-catenin were enhanced in DOP rat vertebrae. Our results suggest that the IGF-1R/β-catenin signaling axis plays a role in the pathogenesis of DOP. This may contribute to development of the underlying therapeutic target for DOP.
Aged ; Animals ; Bone Density ; Diabetes Mellitus, Experimental/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis/etiology* ; Rats ; Receptor, IGF Type 1/physiology* ; Signal Transduction ; Streptozocin ; beta Catenin/physiology*

OBJECTIVETo explore the effects of electroacupuncture (EA) at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency (POI).

METHODSA total of 48 SD female rats with regular estrus were divided into a blank group (=8), a model group (=10), an EA group (=10), a binding group (=10) and a tamoxifen (TAM) group (=10). The rats in the model group, EA group, binding group and TAM group were all treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 15 consecutive days to establish the model of POI; the rats in the blank group were treated with normal diet. After the model was established successfully, the rats in the EA group were treated with EA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) with continuous wave (1 to 3 Hz, 0.1 to 1 mA) for 20 minutes, once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the TAM group were treated with subcutaneous injection of tamoxifen (1mg/kg), once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the binding group were bound by a small sack as the EA group. The rats in the blank group and the model group were treated with normal diet. After four weeks, the sexual gland weight and index were tested in each group; the ELISA method was applied to test the level of anti-mllerian hormone (AMH) and inhibin B; the morphology of ovary was observed; the number of primordial follicles, primary follicle, antral follicle and atretic follicle was counted; the expression of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) were measured.

RESULTS(1) Compared with the blank group, the ovary weight, ovary index, uterus weight and uterus index were significantly decreased after treatment in the model group, EA group, binding group and TAM group (all <0.01); but the differences between the model group and the EA group, binding group, TAM group were not significant (all >0.05). (2) Compared with the blank group, the levels of serum AMH, inhibin B and E were significantly reduced; the levels of FSH and LH were significantly increased in the model group; EA group, binding group and TAM group (all <0.01). Compared with the model group, the levels of serum AMH, inhibin B and E were significantly increased, the level of FSH and LH were significantly reduced in the EA group and TAM group (all <0.01). (3) Compared with the blank group, in the model group, EA group, binding group and TAM group the ovary was dark red and pale, surrounded by particle or not; the morphology was small and atrophic; the primordial follicles was reduced even vanished; the structure of primary follicle was damaged and loosely arranged; the mature follicle was few; the atretic follicle and interstitial gland were increased. (4) Compared with the blank group, the expressions of IGF-1 mRNA and IGF-1R mRNA were increased in the model group (all <0.01); compared with the blank group, the expression of IGF-1 mRNA was increased in the binding group (<0.05), but that of IGF-1R mRNA was not significantly different (>0.05); compared with the model group, the expression of IGF-1 mRNA was not significantly different in the EA group, binding group and TAM group (all >0.05), but that of IGF-1R mRNA was reduced (<0.05, <0.01).

CONCLUSIONEA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) has improvement effect on ovarian function in rats with VCD-induced POI, which is likely to be related to regulating the IGF-1R mRNA expression to improve the IGF-1/ IGF-1R axis.

Acupuncture Points ; Animals ; Electroacupuncture ; Female ; Insulin-Like Growth Factor I ; metabolism ; Primary Ovarian Insufficiency ; chemically induced ; therapy ; Rats ; Rats, Sprague-Dawley ; Receptor, IGF Type 1 ; metabolism ; Tamoxifen ; pharmacology

Survival and migration of transplanted neural stem cells (NSCs) are prerequisites for therapeutic benefits in spinal cord injury. We have shown that survival of NSC grafts declines after transplantation into the injured spinal cord, and that combining treadmill training (TMT) enhances NSC survival via insulin-like growth factor-1 (IGF-1). Here, we aimed to obtain genetic evidence that IGF-1 signaling in the transplanted NSCs determines the beneficial effects of TMT. We transplanted NSCs heterozygous (+/−) for Igf1r, the gene encoding IGF-1 receptor, into the mouse spinal cord after injury, with or without combining TMT. We analyzed the influence of genotype and TMT on locomotor recovery and survival and migration of NSC grafts. In vitro experiments were performed to examine the potential roles of IGF-1 signaling in the migratory ability of NSCs. Mice receiving +/− NSC grafts showed impaired locomotor recovery compared with those receiving wild-type (+/+) NSCs. Locomotor improvement by TMT was more pronounced with +/+ grafts. Deficiency of one allele of Igf1r significantly reduced survival and migration of the transplanted NSCs. Although TMT did not significantly influence NSC survival, it substantially enhanced the extent of migration for only +/+ NSCs. Cultured neurospheres exhibited dynamic motility with cytoplasmic protrusions, which was regulated by IGF-1 signaling. IGF-1 signaling in transplanted NSCs may be essential in regulating their survival and migration. Furthermore, TMT may promote NSC graft-mediated locomotor recovery via activation of IGF-1 signaling in transplanted NSCs. Dynamic NSC motility via IGF-1 signaling may be the cellular basis for the TMT-induced enhancement of migration.
Alleles ; Animals ; Cytoplasm ; Genotype ; In Vitro Techniques ; Insulin-Like Growth Factor I ; Mice ; Neural Stem Cells* ; Receptor, IGF Type 1 ; Spinal Cord Injuries ; Spinal Cord* ; Transplants*

BACKGROUND/AIMS: Statins act as antineoplastic agents through the inhibition of cell proliferation. This study sought to demonstrate the effects of statins on extrahepatic bile duct cancer cell apoptosis and to document the changes in protein expression involved in tumor growth and suppression. METHODS: Human extrahepatic bile duct cancer cells were cultured. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of statins on cell proliferation. Apoptosis was measured by a cell death detection enzyme-linked immunosorbent assay and caspase-3 activity assay, and flow cytometry was used to determine the percentage of cells in each phase of the cell cycle. The protein expression of Bax, Bcl-2, insulin-like growth factor 1 (IGF-1) receptor, extracellular signal-regulated kinase 1/2 (ERK1/2), and Akt was measured by Western blot analysis. RESULTS: Simvastatin suppressed cell proliferation by inducing G1 phase cell cycle arrest in bile duct cancer cells. Furthermore, it induced apoptosis via caspase-3 activation, downregulated the expression of the Bcl-2 protein, and enhanced the expression of the Bax protein. Moreover, simvastatin suppressed the expression of the IGF-1 receptor and IGF-1-induced ERK/Akt activation. CONCLUSIONS: Simvastatin induces apoptosis in bile duct cancer cells, which suggests that it could be an antineoplastic agent for bile duct cancer.
Antineoplastic Agents/pharmacology ; Apoptosis/*drug effects ; Bile Duct Neoplasms/*drug therapy ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Hypolipidemic Agents/*pharmacology ; Receptor, IGF Type 1/*drug effects ; Simvastatin/*pharmacology

The length of IGF1R 3'UTR is greater than 7 kb. The structure of IGF1R 3'UTR is complex, with multiple binding sites of miRNAs. IGF1R is involved in the regulation of MAPK and PI3K/AKT signaling pathways and theformation and development of tumors. Bioinformatics analysis can reveal the structure features of IGF1R, which provides ideas for further research. The analysis shows that the binding sites between IGF1R and miRNAs have the highest mutation rate in Neuroblastoma. We analyzed the structure of 3'UTR, miRNAs binding sites, physical and chemical properties, hydrophilic-hydrophobic property, glycosylation and phosphorylation sites, secondary structure and tertiary structure modeling of IGF1R. The locations and names of amino acids interacting in IGF1R and IGF1 were obtained by molecular docking. Therefore, if IGF1R 3'UTR is mutated, the capacity of IGF1R combined with miRNAs will reduce and the IGF1R expression will be up-regulated, and the function of miRNAs will be repressed. We can change the sites of IGF1R to combine with IGF1 to repress the function of IGF1R and IGF1. Then the function of IGF1R will be repressed.
Binding Sites ; Computational Biology ; Humans ; Insulin-Like Growth Factor I ; MicroRNAs ; chemistry ; Molecular Docking Simulation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptor, IGF Type 1 ; chemistry ; Signal Transduction

Klotho functions as a tumor suppressor predominantly expressed in renal tubular cells, the origin of clear cell renal cell carcinoma (ccRCC). Altered expression and/or activity of growth factor receptor have been implicated in ccRCC development. Although Klotho suppresses a tumor progression through growth factor receptor signaling including insulin-like growth factor-1 receptor (IGF-1R), the role of Klotho acting on IGF-1R in ccRCC and its clinical relevance remains obscure. Here, we show that Klotho is favorable prognostic factor for ccRCC and exerts tumor suppressive role for ccRCC through inhibiting IGF-1R signaling. Our data shows the following key findings. First, in tumor tissues, the level of Klotho and IGF-1R expression are low or high, respectively, compared to that of adjacent non-neoplastic parenchyma. Second, the Klotho expression is clearly low in higher grade of ccRCC and is closely associated with clinical outcomes in tumor progression. Third, Klotho suppresses IGF-1-stimulated cell proliferation and migration by inhibiting PI3K/Akt pathway. These results provide compelling evidence supporting that Klotho acting on IGF-1R signaling functions as tumor suppressor in ccRCC and suggest that Klotho is a potential carcinostatis substance for ccRCC.
Carcinoma, Renal Cell* ; Cell Proliferation ; Prognosis ; Receptor, IGF Type 1