Akromegália je raritné endokrinologické ochorenie charakterizované nadprodukciou rastového hormónu (RH), najčastej- šie na podklade adenómu hypofýzy s následnou zvýšenou produkciou inzulínu podobného rastového faktora 1 (IGF-1) v pečeni. Účinky RH a IGF-1 na metabolizmus glukózy sú antagonistické; RH vyvoláva inzulínovú rezistenciu, zatiaľ čo IGF-1 zvyšuje inzulínovú citlivosť. Avšak inzulín-antagonizujúci účinok RH prevyšuje inzulín-senzitizujúci účinok IGF-1 v cieľových tkanivách, čo vedie k vzniku diabetes mellitus (DM) pri akromegálii. Sekundárny DM je častou komplikáciou u pacientov s akromegáliou. DM môže byť prvým prejavom ochorenia, pretože hyperglykémia spôsobená inzulínovou rezistenciou býva často významná. Diagnostika a liečba DM u pacientov s akromegáliou je komplexná a vyžaduje multidisciplinárny prístup, ktorý zahŕňa endokrinológov, diabetológov a ďalších špecialistov. Účinná kontrola akromegálie prostredníctvom chirurgického zákroku, farmakoterapie alebo rádioterapie môže zlepšiť glukózovú homeostázu a znížiť riziko komplikácií spojených s DM. Uvedený prehľadový článok sa zaoberá patofyziologickými a klinickými zvláštnosťami DM u pacientov s akromegáliou, ako aj potenciálnymi účinkami špecifickej liečby akromegálie na glukózovú homeostázu.
Acromegaly is a rare endocrine disorder characterized by the overproduction of growth hormone (GH), most commonly due to a pituitary adenoma, leading to increased production of insulin-like growth factor 1 (IGF-1) in the liver. The effects of GH and IGF-1 on glucose metabolism are antagonistic; GH induces insulin resistance, while IGF-1 enhances insulin sensitivity. However, the insulin-antagonizing effect of GH outweighs the insulin-sensitizing effect of IGF-1 in target tissues, leading to the development of diabetes mellitus (DM) in acromegaly.Secondary DM is a frequent complication in patients with acromegaly. In fact, DM may be the first manifestation of the disease, because hyperglycemia caused by insulin resistance is often significant. The diagnosis and management of DM in patients with acromegaly are complex and require a multidisciplinary approach involving endocrinologists, diabetologists, and other specialists. Effective control of acromegaly through surgery, pharmacotherapy, or radiotherapy can improve glucose homeostasis and reduce the risk of complications associated with DM. This review article discusses the pathophysiological and clinical characteristics of DM in patients with acromegaly, as well as the potential effects of specific acromegaly treatments on glucose homeostasis.
- MeSH
- Acromegaly * diagnosis etiology drug therapy MeSH
- Diabetes Mellitus etiology MeSH
- Dopamine analogs & derivatives MeSH
- Glucose metabolism MeSH
- Insulin-Like Growth Factor I metabolism MeSH
- Insulin Resistance MeSH
- Humans MeSH
- Growth Hormone analogs & derivatives blood MeSH
- Blood Glucose Self-Monitoring MeSH
- Somatostatin analogs & derivatives MeSH
- Check Tag
- Humans MeSH
AIMS: Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. METHODS: High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. RESULTS: We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. CONCLUSION: Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.
- MeSH
- Pancreatitis, Chronic * metabolism blood MeSH
- Diabetes Mellitus, Type 2 * metabolism MeSH
- Adult MeSH
- Carcinoma, Pancreatic Ductal metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Pancreatic Neoplasms * metabolism blood MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Tretinoin * metabolism blood MeSH
- Vitamin A * blood metabolism MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Inzulinu podobný růstový faktor 2 patří, spolu s několika dalšími inzulinu podobnými peptidy, do evolučně konzervované rodiny signalizačních molekul, které jsou nezbytné pro normální buněčnou proliferaci a vývoj mozku. Dřívější studie se zaměřovaly převážně na jeho úlohu v embryonálním vývoji a kancerogenezi. V posledních letech byly odhaleny nové poznatky týkající se role inzulinu podobného růstového faktoru 2 v centrální nervové soustavě, zejména jeho význam pro učení, konsolidaci paměti a zlepšení kognitivních funkcí. I přes stále ne zcela prozkoumanou fyziologickou roli inzulinu podobného růstového faktoru 2 se v našem článku snažíme podrobněji popsat a vysvětlit jeho známé funkce a diskutovat jeho potenciální využití, včetně možné aplikace v léčbě neurodegenerativních onemocnění.
Insulin-like growth factor 2 (IGF2), along with several other insulin-like peptides, belongs to an evolutionarily conserved family of signalling molecules essential for normal cell proliferation and brain development. Previous studies have mainly focused on its role in embryonic development and carcinogenesis. In recent years, new insights revealed the role of IGF2 in the central nervous system, particularly its importance in learning, memory consolidation and enhancement. Despite the still not fully explored physiological role of IGF2, in this article we aim to describe and explain its known functions in more detail and discuss its potential uses, including its possible application in the treatment of neurodegenerative diseases.
- MeSH
- Gene Expression genetics MeSH
- Insulin-Like Growth Factor II * physiology genetics metabolism ultrastructure MeSH
- Insulin physiology MeSH
- Carcinogenesis genetics metabolism MeSH
- Cognition physiology MeSH
- Humans MeSH
- Neurodegenerative Diseases etiology genetics classification MeSH
- Receptor, IGF Type 2 physiology metabolism ultrastructure MeSH
- Receptor, Insulin physiology genetics ultrastructure MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The purpose of this study was to determine the effects of resistance training (RT) alongside creatine-hydrochloride (Cr-HCl) or creatine monohydrate (CrM) supplementation on anabolic/catabolic hormones, strength, and body composition. Forty participants with an age range of 18-25 years were randomly divided into four groups (n=10): RT+Cr-HCl (0.03 g.kg-1 of body mass), RT+CrM-loading phase (CrM-LP) (0.3 g.kg-1 of body mass for five days (loading) and 0.03 g.kg-1 body mass for 51 days (maintenance)), RT+CrM-without loading phase (CrM-WLP) (0.03 g.kg-1 body mass), and RT+placebo (PL). The participants consumed supplements and performed RT with an intensity of 70-85 % 1RM for eight weeks. Before and after the training and supplementation period, strength (1RM), body composition (percent body fat (PBF), skeletal muscle mass (SMM), muscular cross-sectional area (MCSA)) and serum levels of testosterone, growth hormone (GH), insulin-like growth factor-1 (IGF-1), cortisol, adrenocorticotropic hormone (ACTH), follistatin and myostatin were measured. The results showed that in the supplementation groups, strength, arm and thigh MCSA, and SMM significantly increased, and PBF significantly decreased (P
- MeSH
- Adult MeSH
- Hydrocortisone blood MeSH
- Insulin-Like Growth Factor I metabolism MeSH
- Muscle, Skeletal metabolism drug effects MeSH
- Creatine * MeSH
- Humans MeSH
- Human Growth Hormone blood MeSH
- Adolescent MeSH
- Young Adult MeSH
- Resistance Training * methods MeSH
- Dietary Supplements * MeSH
- Body Composition * MeSH
- Muscle Strength * drug effects MeSH
- Testosterone blood MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
Preptin, a 34-amino acid peptide derived from pro-IGF2, is believed to influence various physiological processes, including insulin secretion and the regulation of bone metabolism. Despite its recognized involvement, the precise physiological role of preptin remains enigmatic. To address this knowledge gap, we synthesized 16 analogs of preptin, spanning a spectrum from full-length forms to fragments, and conducted comprehensive comparative activity evaluations alongside native human, mouse and rat preptin. Our study aimed to elucidate the physiological role of preptin. Contrary to previous indications of broad biological activity, our thorough analyses across diverse cell types revealed no significant biological activity associated with preptin or its analogs. This suggests that the associations of preptin with various diseases or tissue-specific abundance fluctuations may be influenced by factors beyond preptin itself, such as higher levels of IGF2 or IGF2 proforms present in tissues. In conclusion, our findings challenge the conventional notion of preptin as an isolated biologically active molecule and underscore the complexity of its interactions within biological systems. Rather than acting independently, the observed effects of preptin may arise from experimental conditions, elevated preptin concentrations, or interactions with related molecules such as IGF2.
- MeSH
- Insulin-Like Growth Factor II * metabolism MeSH
- Insulin metabolism MeSH
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Peptide Fragments metabolism MeSH
- Protein Precursors metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
V tomto článku sa venujeme endokrinne sprostredkovanej osteoporóze spôsobenej poruchami sekrécie rastového hormónu (RH); nedostatku rastového hormónu u dospelých a akromegálii. RH a inzulínu podobný rastový faktor-1 (IGF-1) stimulujú lineárny rast kostí prostredníctvom komplexných hormonálnych interakcií a aktivujú epifýzové prechondrocyty. GH prostredníctvom receptorového aktivátora jadrového faktora-kappaB (RANK), jeho ligandu (RANK-L) a osteoprotegerínového systému stimuluje produkciu osteoprotegerínu a jeho akumuláciu v kostnej matrici. Nesprávna funkcia tohto mechanizmu môže viesť k špecifickému poškodeniu kostí. Primárnym problémom kostného postihnutia pri poruchách sekrécie rastového hormónu je riziko osteoporotických fraktúr, preto je dôležité posúdiť kvalitu kosti, ktorá lepšie odráža skutočnú predispozíciu pacienta na fraktúru. Metódou odhadu kvality kostí z DXA skenov bedrovej chrbtice je trabekulárne kostné skóre (TBS). Pri akromegálii TBS lepšie definuje riziko zlomeniny, pretože BMD je normálna alebo dokonca zvýšená. TBS pomáha sledovať efekt liečby rastovým hormónom a vitamínom D. Napriek týmto zisteniam by sa TBS nemal používať samostatne, ale je potrebné komplexné zváženie všetkých rizikových faktorov zlomenín, BMD a markerov kostného obratu.
In this article, we address endocrine-mediated osteoporosis caused by disorders of growth hormone (GH) secretion; growth hormone deficiency in adults and acromegaly. GH and insulin-like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activate epiphyseal prechondrocytes. GH stimulates the production of osteoprotegerin and its accumulation in the bone matrix through the receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L) and the osteoprotegerin system. Incorrect function of this mechanism can lead to specific bone damage. The primary problem of bone involvement in disorders of GH secretion is the risk of osteoporotic fractures, so it is important to assess the quality of the bone, which better reflects the actual predisposition of the patient to fracture. The method for estimating bone quality from DXA scans of the lumbar spine is the trabecular bone score (TBS). In acromegaly, TBS better defines fracture risk because BMD is normal or even elevated. TBS helps to monitor the effect of treatment with growth hormone and vitamin D. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and markers of bone turnover is required.
- Keywords
- trabekulární kostní skóre,
- MeSH
- Absorptiometry, Photon methods MeSH
- Acromegaly diagnosis complications MeSH
- Insulin-Like Growth Factor I deficiency MeSH
- Bone Density * drug effects MeSH
- Humans MeSH
- Osteoporotic Fractures etiology prevention & control MeSH
- Osteoporosis etiology MeSH
- Growth Hormone * deficiency therapeutic use MeSH
- Vitamin D therapeutic use MeSH
- Check Tag
- Humans MeSH
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.
- MeSH
- CA-19-9 Antigen * blood MeSH
- Antigens, Neoplasm blood MeSH
- Adult MeSH
- Insulin-Like Growth Factor I metabolism MeSH
- Carcinoembryonic Antigen * blood MeSH
- Keratin-19 blood MeSH
- Keratins blood MeSH
- Colorectal Neoplasms * blood diagnosis pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * blood MeSH
- Peptides MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- ROC Curve MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Thymidine Kinase * blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.
- MeSH
- Risk Assessment methods MeSH
- Insulin-Like Growth Factor Binding Protein 3 blood MeSH
- Insulin-Like Growth Factor I * metabolism MeSH
- Carcinoma, Transitional Cell surgery blood pathology mortality MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor blood MeSH
- Nephroureterectomy * methods MeSH
- Insulin-Like Peptides MeSH
- Preoperative Period MeSH
- Prognosis MeSH
- Insulin-Like Growth Factor Binding Protein 2 * blood MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Urologic Neoplasms surgery blood pathology mortality MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
INTRODUCTION: Among children born small for gestational age, 10-15% fail to catch up and remain short (SGA-SS). The underlying mechanisms are mostly unknown. We aimed to decipher genetic aetiologies of SGA-SS within a large single-centre cohort. METHODS: Out of 820 patients treated with growth hormone (GH), 256 were classified as SGA-SS (birth length and/or birth weight <-2 SD for gestational age and life-minimum height <-2.5 SD). Those with the DNA triplet available (child and both parents) were included in the study (176/256). Targeted testing (karyotype/FISH/MLPA/specific Sanger sequencing) was performed if a specific genetic disorder was clinically suggestive. All remaining patients underwent MS-MLPA to identify Silver-Russell syndrome, and those with unknown genetic aetiology were subsequently examined using whole-exome sequencing or targeted panel of 398 growth-related genes. Genetic variants were classified using ACMG guidelines. RESULTS: The genetic aetiology was elucidated in 74/176 (42%) children. Of these, 12/74 (16%) had pathogenic or likely pathogenic (P/LP) gene variants affecting pituitary development (LHX4, OTX2, PROKR2, PTCH1, POU1F1), the GH-IGF-1 or IGF-2 axis (GHSR, IGFALS, IGF1R, STAT3, HMGA2), 2/74 (3%) the thyroid axis (TRHR, THRA), 17/74 (23%) the cartilaginous matrix (ACAN, various collagens, FLNB, MATN3), and 7/74 (9%) the paracrine chondrocyte regulation (FGFR3, FGFR2, NPR2). In 12/74 (16%), we revealed P/LP affecting fundamental intracellular/intranuclear processes (CDC42, KMT2D, LMNA, NSD1, PTPN11, SRCAP, SON, SOS1, SOX9, TLK2). SHOX deficiency was found in 7/74 (9%), Silver-Russell syndrome in 12/74 (16%) (11p15, UPD7), and miscellaneous chromosomal aberrations in 5/74 (7%) children. CONCLUSIONS: The high diagnostic yield sheds a new light on the genetic landscape of SGA-SS, with a central role for the growth plate with substantial contributions from the GH-IGF-1 and thyroid axes and intracellular regulation and signalling.
- MeSH
- Child MeSH
- Gestational Age MeSH
- Infant, Small for Gestational Age MeSH
- Insulin-Like Growth Factor I MeSH
- Humans MeSH
- Human Growth Hormone * genetics MeSH
- Dwarfism * MeSH
- Infant, Newborn MeSH
- Growth Disorders genetics diagnosis MeSH
- Short Stature Homeobox Protein MeSH
- Silver-Russell Syndrome * genetics MeSH
- Body Height genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
In this article, we focused on the impact of precisely chemically modified FLI maturation medium enriched with fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), insulin-like growth factor 1 (IGF1), and polyvinyl alcohol (PVA) and its potential to improve the efficiency of in vitro production of porcine embryos. We hypothesized that enhancing the composition of the maturation medium could result in an elevated production of embryos in vitro and can affect EGA. FLI medium resulted in a significantly higher rate of oocyte blastocyst maturation and formation compared to the control DMEM medium. In addition, immunocytochemical labelling confirmed the detection of UBF in 4-cell FLI parthenogenic embryos, suggesting similarities with natural embryo development. Through RNAseq analysis, upregulated genes present in 4-cell FLI embryos were found to play key roles in important biological processes such as cell proliferation, cell differentiation, and transcriptional regulation. Based on our findings, we demonstrated the positive influence of FLI medium in the evaluation of in vitro embryo production, EGA detection, transcriptomic and proteomic profile, which was confirmed by the positive activation of the embryonal genome in the 4-cell stage of parthenogenetically activated embryos.
- MeSH
- Blastocyst drug effects metabolism MeSH
- Fertilization in Vitro MeSH
- Fibroblast Growth Factor 2 * pharmacology MeSH
- Insulin-Like Growth Factor I * pharmacology MeSH
- Culture Media * chemistry pharmacology MeSH
- Leukemia Inhibitory Factor * pharmacology MeSH
- Oocytes MeSH
- Swine embryology genetics MeSH
- Proteomics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
