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Endocrinology May 2024
Correction to: "Liver-Specific GH Receptor Gene-Disrupted (LiGHRKO) Mice Have Decreased Endocrine IGF-I, Increased Local IGF-I, and Altered Body Size, Body Composition, and Adipokine Profiles".
Topics: Animals; Mice; Insulin-Like Growth Factor I; Liver; Adipokines; Body Composition; Mice, Knockout; Receptors, Somatotropin; Body Size
PubMed: 38935339
DOI: 10.1210/endocr/bqae065 -
International Journal of Molecular... Jun 2024The role of adipose mesenchymal stem cells (Ad-MSCs) in metabolic syndrome remains unclear. We aimed to assess the expression of selected microRNAs in Ad-MSCs of...
The role of adipose mesenchymal stem cells (Ad-MSCs) in metabolic syndrome remains unclear. We aimed to assess the expression of selected microRNAs in Ad-MSCs of non-diabetic adults in relation to Ad-MSC secretion of protein regulators and basic metabolic parameters. Ten obese, eight overweight, and five normal weight subjects were enrolled: 19 females and 4 males; aged 43.0 ± 8.9 years. Ad-MSCs were harvested from abdominal subcutaneous fat. Ad-MSC cellular expressions of four microRNAs (2 values) and concentrations of IL-6, IL-10, VEGF, and IGF-1 in the Ad-MSC-conditioned medium were assessed. The expressions of miR-21, miR-122, or miR-192 did not correlate with clinical parameters (age, sex, BMI, visceral fat, HOMA-IR, fasting glycemia, HbA1c, serum lipids, CRP, and eGFR). Conversely, the expression of miR-155 was lowest in obese subjects (3.69 ± 2.67 × 10 vs. 7.07 ± 4.42 × 10 in overweight and 10.25 ± 7.05 × 10 in normal weight ones, = 0.04). The expression of miR-155 correlated inversely with BMI (sex-adjusted r = -0.64; < 0.01), visceral adiposity (r = -0.49; = 0.03), and serum CRP (r = -0.63; < 0.01), whereas it correlated positively with serum HDL cholesterol (r = 0.51; = 0.02). Moreover, miR-155 synthesis was associated marginally negatively with Ad-MSC secretion of IGF-1 (r = -0.42; = 0.05), and positively with that of IL-10 (r = 0.40; = 0.06). Ad-MSC expression of miR-155 appears blunted in visceral obesity, which correlates with Ad-MSC IGF-1 hypersecretion and IL-10 hyposecretion, systemic microinflammation, and HDL dyslipidemia. Ad-MSC studies in metabolic syndrome should focus on miR-155.
Topics: Humans; MicroRNAs; Female; Male; Metabolic Syndrome; Mesenchymal Stem Cells; Adult; Middle Aged; Adipose Tissue; Insulin-Like Growth Factor I; Obesity; Interleukin-10; Gene Expression Regulation; Vascular Endothelial Growth Factor A
PubMed: 38928349
DOI: 10.3390/ijms25126644 -
International Journal of Molecular... Jun 2024Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to... (Randomized Controlled Trial)
Randomized Controlled Trial
Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at < 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions.
Topics: Humans; Female; Male; Insulin-Like Growth Factor Binding Protein 1; Middle Aged; Insulin-Like Growth Factor I; Aged; Adult; Life Style; Diabetes Mellitus, Type 2; Biomarkers; Aged, 80 and over; Prediabetic State; Intra-Abdominal Fat; Insulin-Like Growth Factor Binding Protein 2
PubMed: 38928106
DOI: 10.3390/ijms25126400 -
Anticancer Research Jul 2024Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management...
BACKGROUND/AIM
Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis.
PATIENTS AND METHODS
This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival.
RESULTS
Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413.
CONCLUSION
The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.
Topics: Humans; Thymidine Kinase; Colorectal Neoplasms; Biomarkers, Tumor; Male; Female; Aged; Middle Aged; Carcinoembryonic Antigen; Retrospective Studies; Prognosis; CA-19-9 Antigen; ROC Curve; Insulin-Like Growth Factor I; Keratins; Adult; Aged, 80 and over; Keratin-19; Case-Control Studies; Antigens, Neoplasm; Peptides
PubMed: 38925804
DOI: 10.21873/anticanres.17124 -
Reproduction in Domestic Animals =... Jun 2024Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high...
Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high dropout rate of reared bulls is a problem for AI centres. Potential hormonal indicators of bull sexual maturation (cortisol, dehydroepiandrosterone (DHEA), testosterone, oestradiol, insulin-like growth factor 1 (IGF-1)) were observed and evaluated in relation to the performance parameters to perhaps identify candidate biomarkers allowing an early selection of bulls as suitable sires. Blood samples from 102 German Holstein calves at 4 ± 1, 8 ± 1 and 12 ± 2 months of age from six AI centres were analysed using validated immunoassays for cortisol, DHEA, testosterone, oestradiol and IGF-1. Semen analyses included native and thawed diluted semen. Bulls were classified at the first semen collection into groups with good versus poor performance (GP vs. LP). After 2 years, the subsequent differentiation was done in high (HPP), medium (MPP) and low performance persistency (LPP). Age at first semen collection was an important factor for sperm quality. Cortisol concentrations decreased with age, but the cortisol/DHEA ratio decreased with age only in GP bulls (p < .05). Oestradiol and testosterone concentrations both correlated with libido behaviour (p < .05). Testosterone and IGF-1 concentrations were higher at the time of first semen collection in GP bulls and increased with age (p < .05). In conclusion, testosterone and IGF-1 concentrations at first semen collection are associated with performance at first semen collection and future performance persistency, and might be useful early biomarkers for consistent sperm producing bulls on AI centres.
Topics: Animals; Male; Cattle; Insemination, Artificial; Biomarkers; Semen Analysis; Estradiol; Testosterone; Insulin-Like Growth Factor I; Hydrocortisone; Sexual Maturation; Semen; Dehydroepiandrosterone
PubMed: 38923114
DOI: 10.1111/rda.14646 -
BMC Endocrine Disorders Jun 2024An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary...
PURPOSE
An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index.
METHODS
We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55).
RESULTS
IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04).
CONCLUSIONS
Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.
Topics: Humans; Prolactinoma; Insulin-Like Growth Factor I; Female; Male; Adult; Retrospective Studies; Dopamine Agonists; Pituitary Neoplasms; Middle Aged; Cabergoline; Body Weight; Follow-Up Studies; Prolactin; Body Mass Index; Prognosis
PubMed: 38902646
DOI: 10.1186/s12902-024-01622-4 -
Revista Da Associacao Medica Brasileira... 2024
Topics: Humans; Fibromyalgia; Leptin; Insulin-Like Growth Factor I; Biomarkers; Insulin-Like Peptides
PubMed: 38896736
DOI: 10.1590/1806-9282.20240005 -
Molecules (Basel, Switzerland) Jun 2024The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating...
The existing kinase inhibitors for hepatocellular carcinoma (HCC) have conferred survival benefits but are hampered by adverse effects and drug resistance, necessitating the development of novel agents targeting distinct pathways. To discover potent new anti-HCC compounds, we leveraged scaffold hopping from Sorafenib and introduced morpholine/piperidine moieties to develop ureido-substituted 4-phenylthiazole analogs with optimized physicochemical properties and binding interactions. Notably, compound exhibited potent cytotoxicity against HepG2 cells (IC = 0.62 ± 0.34 μM), significantly exceeding Sorafenib (IC = 1.62 ± 0.27 μM). Mechanistic investigations revealed that compound potently inhibited HCC cell migration and colony formation, and it induced G2/M arrest and early-stage apoptosis. Kinase profiling revealed IGF1R as a key target, which compound potently inhibited (76.84% at 10 μM). Molecular modeling substantiated compound 's strong binding to IGF1R via multiple hydrogen bonds. Computational predictions indicate favorable drug-like properties for compound . These findings provide a promising drug candidate for the treatment of HCC patients.
Topics: Humans; Receptor, IGF Type 1; Cell Proliferation; Hep G2 Cells; Thiazoles; Protein Kinase Inhibitors; Antineoplastic Agents; Apoptosis; Liver Neoplasms; Carcinoma, Hepatocellular; Cell Movement; Structure-Activity Relationship; Molecular Docking Simulation; Receptors, Somatomedin; Molecular Structure; Cell Line, Tumor; Sorafenib; Models, Molecular
PubMed: 38893528
DOI: 10.3390/molecules29112653 -
Nutrients May 2024The gut microbiota plays a crucial role in postnatal growth, particularly in modulating the development of animals during their growth phase. In this study, we...
The gut microbiota plays a crucial role in postnatal growth, particularly in modulating the development of animals during their growth phase. In this study, we investigated the effects of antibiotic-induced dysbiosis of the gut microbiota on the growth of weaning rats by administering a non-absorbable antibiotic cocktail (ABX) in water for 4 weeks. ABX treatment significantly reduced body weight and feed intake in rats. Concurrently, ABX treatment decreased microbial abundance and diversity in rat ceca, predominantly suppressing microbes associated with bile salt hydrolase (BSH) activity. Furthermore, decreased appetite may be attributed to elevated levels of glucagon-like peptide-1 (GLP-1) in the serum, along with reduced neuropeptide Y (NPY) and increased cocaine and amphetamine-regulated transcript (CART) in the hypothalamus at the mRNA level. Importantly, concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) were decreased in the serum and liver of antibiotic-treated rats. These alterations were associated with significant down-regulation of IGF-2 mRNA in the liver and significantly decreased farnesoid X receptor (FXR) protein expression and binding to the IGF-2 promoter. These results indicate that antibiotic-induced gut microbial dysbiosis not only impacts bile acid metabolism but also diminishes rat growth through the FXR-mediated IGF-2 pathway.
Topics: Animals; Gastrointestinal Microbiome; Dysbiosis; Receptors, Cytoplasmic and Nuclear; Liver; Anti-Bacterial Agents; Weaning; Rats; Male; Insulin-Like Growth Factor II; Rats, Sprague-Dawley; Body Weight
PubMed: 38892577
DOI: 10.3390/nu16111644 -
International Journal of Molecular... May 2024Dysregulation of the insulin-like growth factor (IGF) system determines the onset of various pathological conditions, including cancer. Accordingly, therapeutic... (Review)
Review
Dysregulation of the insulin-like growth factor (IGF) system determines the onset of various pathological conditions, including cancer. Accordingly, therapeutic strategies have been developed to block this system in tumor cells, but the results of clinical trials have been disappointing. After decades of research in the field, it is safe to say that one of the major reasons underlying the poor efficacy of anti-IGF-targeting agents is derived from an underestimation of the molecular complexity of this axis. Genetic, transcriptional, post-transcriptional and functional interactors interfere with the activity of canonical components of this axis, supporting the need for combinatorial approaches to effectively block this system. In addition, cancer cells interface with a multiplicity of factors from the extracellular compartment, which strongly affect cell destiny. In this review, we will cover novel extracellular mechanisms contributing to IGF system dysregulation and the implications of such dangerous liaisons for cancer hallmarks and responses to known and new anti-IGF drugs. A deeper understanding of both the intracellular and extracellular microenvironments might provide new impetus to better decipher the complexity of the IGF axis in cancer and provide new clues for designing novel therapeutic approaches.
Topics: Humans; Neoplasms; Animals; Tumor Microenvironment; Somatomedins; Signal Transduction; Antineoplastic Agents
PubMed: 38892104
DOI: 10.3390/ijms25115915