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International Journal of Molecular... Jun 2021It has been well established that insulin-like growth factors (IGFs) mainly mediate long-term actions in cell fates, whereas insulin predominantly exerts its role on... (Review)
Review
It has been well established that insulin-like growth factors (IGFs) mainly mediate long-term actions in cell fates, whereas insulin predominantly exerts its role on metabolic activity. Indeed, insulin mediates multiple anabolic biological activities in glucose and amino acid transport, lipid and protein synthesis, the induction of glycogen, the inhibition of gluconeogenesis, lipolysis, and protein degradation. The interactions and differences between insulin receptor signaling and IGF-I receptor signaling in the metabolism and the cell fates are quite complicated. Because of the overlapping actions of IGF-I singling with insulin signaling, it has been difficult to distinguish the role of both signaling mechanisms on the metabolism. Furthermore, comprehensive information on the IGF-I function in respective tissues remains insufficient. Therefore, we need to clarify the precise roles of IGF-I signaling on the metabolism separate from those of insulin signaling. This review focuses on the metabolic roles of IGFs in the respective tissues, especially in terms of comparison with those of insulin, by overviewing the metabolic phenotypes of tissue-specific IGF-I and insulin receptor knockout mice, as well as those in mice treated with the dual insulin receptor/IGF-I receptor inhibitor OSI-906.
Topics: Animals; Energy Metabolism; Gene Expression Regulation; Humans; Insulin; Mice; Organ Specificity; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction; Somatomedins
PubMed: 34202916
DOI: 10.3390/ijms22136817 -
The British Journal of Cancer.... Dec 1988The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that... (Review)
Review
The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Cell Nucleus; Cells, Cultured; Female; Insulin; Lactation; Mammary Glands, Animal; Phosphatidylinositols; Pregnancy; Receptors, Cell Surface; Receptors, Somatomedin; Somatomedins
PubMed: 2855464
DOI: No ID Found -
The American Journal of Clinical... Sep 2007An accumulating body of epidemiologic and laboratory evidence suggests that insulin and insulin-like growth factors influence both the risk and the prognosis of cancer.... (Review)
Review
An accumulating body of epidemiologic and laboratory evidence suggests that insulin and insulin-like growth factors influence both the risk and the prognosis of cancer. In this brief review, I highlight topics covered in my lecture on research directions in this field, including the view that metformin deserves investigation as a potential adjunct in the treatment or prevention of cancer in persons with hyperinsulinemia.
Topics: Diabetes Complications; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Life Style; Metformin; Neoplasms; Obesity; Prognosis; Risk Factors; Somatomedins
PubMed: 18265475
DOI: 10.1093/ajcn/86.3.820S -
Poultry Science Aug 1991It is generally thought that growth factors play a major role in regulating proliferation and differentiation of myogenic cells. Cell culture studies indicate that of... (Review)
Review
It is generally thought that growth factors play a major role in regulating proliferation and differentiation of myogenic cells. Cell culture studies indicate that of the known growth factors, the fibroblast growth factors, the transforming growth factor beta, and the insulin-like growth factor families play the most significant roles in this process. The fibroblast growth factors stimulate proliferation and inhibit differentiation of most cultured myogenic cells. Insulin-like growth factors also stimulate proliferation of myogenic cells, but, in contrast to the fibroblast growth factors, the insulin-like growth factors also stimulate differentiation. Transforming growth factor beta inhibits differentiation of cultured myogenic cells. There are conflicting reports as to its effect on proliferation. The combined effects of these growth factors in vivo may play a major role in determining the rate of proliferation and differentiation of muscle tissue.
Topics: Animals; Cell Differentiation; Cell Division; Fibroblast Growth Factors; Muscle Development; Muscles; Somatomedins; Transforming Growth Factor beta
PubMed: 1924098
DOI: 10.3382/ps.0701815 -
Experimental Diabesity Research 2003The IGF system plays vital roles in neuronal development, metabolism, regeneration and survival. It consists of IGF-I, IGF-II, insulin, IGF-I-receptor, and those of... (Review)
Review
The IGF system plays vital roles in neuronal development, metabolism, regeneration and survival. It consists of IGF-I, IGF-II, insulin, IGF-I-receptor, and those of IGF-II and insulin as well as IGF-binding proteins. In the last decades it has become clear that perturbations of the IGF system play important roles in the pathogenesis of diabetic neurological complications. In the peripheral nervous system IGF-I, insulin, and C-peptide particularly in type 1 diabetes participate in the development of axonal degenerative changes and contributes to impaired regenerative capacities. These abnormalities of the IGF system appear to be less pronounced in type 2 diabetes, which may in part account for the relatively milder neurological complications in this type of diabetes. The members of the IGF system also provide anti-apoptotic effects on both peripheral and central nervous system neurons. Furthermore, both insulin and C-peptide and probably IGF-I possess gene regulatory capacities on myelin constituents and axonal cytoskeletal proteins. Therefore, replenishment of various members of the IGF system provides a reasonable rational for prevention and treatment of diabetic neurological complications.
Topics: Animals; Central Nervous System Diseases; Diabetic Neuropathies; Humans; Peripheral Nervous System Diseases; Somatomedins
PubMed: 14668047
DOI: 10.1155/EDR.2003.235 -
The Journal of Clinical Endocrinology... Sep 2020Insulin-like growth factor (IGF) signaling is crucial for sex differentiation and development of Leydig and Sertoli cells in fetal mice testes. No such information is...
CONTEXT
Insulin-like growth factor (IGF) signaling is crucial for sex differentiation and development of Leydig and Sertoli cells in fetal mice testes. No such information is available for human embryonic and fetal testes and ovaries.
OBJECTIVE
To investigate presence and activity of the IGF signaling system during human embryonic and fetal ovarian and testicular development.
DESIGN
Human embryonic and fetal gonads were obtained following legal terminations of pregnancies. Gene expression was assessed by microarray and qPCR transcript analyses. Proteins of the IGF system components were detected with immunohistochemistry and immunofluorescence analyses. Specimens were included from 2010 to 2017.
SETTING
University Hospital.
PATIENTS/PARTICIPANTS
Ovaries and testes from a total of 124 human embryos and fetuses aged 5 to 17 postconception weeks were obtained from healthy women aged 16 to 47 years resident in Denmark or Scotland.
MAIN OUTCOME MEASURES
Gene expression analysis using microarray was performed in 46 specimens and qPCR analysis in 56 specimens, both sexes included. Protein analysis included 22 specimens (11 ovaries, 11 testes).
RESULTS
IGF system members were detected in embryonic and fetal testes and ovaries, both at gene transcript and protein level. A higher expression of IGF regulators was detected in testes than ovaries, with a preferred localization to Leydig cells.
CONCLUSIONS
These data indicate that the IGF system is active during very early gestation, when it may have a regulatory role in Leydig cells.
Topics: Adolescent; Adult; Embryo, Mammalian; Female; Fetus; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gestational Age; Gonads; Humans; Insulin-Like Growth Factor Binding Proteins; Male; Microarray Analysis; Middle Aged; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Receptors, Somatomedin; Signal Transduction; Somatomedins; Young Adult
PubMed: 32726409
DOI: 10.1210/clinem/dgaa470 -
Endocrinology and Metabolism Clinics of... Jun 1999Insulin-like growth factors, their receptors, binding proteins, and binding protein proteases are important in normal and abnormal ovarian follicle development. IGFs... (Review)
Review
Insulin-like growth factors, their receptors, binding proteins, and binding protein proteases are important in normal and abnormal ovarian follicle development. IGFs stimulate ovarian cellular mitosis and steroidogenesis and inhibit apoptosis. Patterns of expression of IGF family members are characteristic of whether follicles are estrogen- or androgen-dominant. The PCOS follicle is androgen-dominant but does not appear to be atretic and has characteristic IGF family expression. Available data strongly support an intraovarian, as opposed to endocrine, role for this growth factor family in ovarian follicle growth, steroidogenesis, and atresia.
Topics: Female; Follicular Fluid; Humans; Insulin-Like Growth Factor Binding Proteins; Ovary; Polycystic Ovary Syndrome; Receptors, Somatomedin; Somatomedins
PubMed: 10352921
DOI: 10.1016/s0889-8529(05)70072-4 -
International Journal of Molecular... Sep 2017Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced... (Review)
Review
Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced in the developing brain. In this paper we will try to give an answer to the following questions: Why are studies in children important? What clinical studies in neonatal asphyxia, infantile spasms, progressive encephalopathy-hypsarrhythmia-optical atrophy (PEHO) syndrome, infantile ceroid lipofuscinosis (INCL), autistic spectrum disorders (ASD) and subacute sclerosing encephalopathy (SSPE) have been carried out? What are IGF-based therapeutic strategies? What are the therapeutic approaches? We conclude that there are now great hopes for the therapeutic use of IGF-1 for some neurological disorders (particularly ASD).
Topics: Age Factors; Animals; Child; Child, Preschool; Clinical Studies as Topic; Disease Susceptibility; Humans; Insulin-Like Growth Factor I; Molecular Targeted Therapy; Nervous System Diseases; Neurogenesis; Somatomedins; Treatment Outcome
PubMed: 28954393
DOI: 10.3390/ijms18102056 -
Archives of Disease in Childhood Apr 1974A child presenting with the clinical features of hyposomatotropism but with high immunoreactive plasma growth hormone is described. During short-term administration of...
A child presenting with the clinical features of hyposomatotropism but with high immunoreactive plasma growth hormone is described. During short-term administration of human growth hormone (HGH) his response with regard to fasting blood-glucose and free fatty acids, plasma-somatomedin, urinary excretion of calcium, nitrogen, and hydroxyproline was minimal or absent. 6 months of treatment with HGH did not reduce the endogenous HGH secretion. Insulin secretion had not increased and plasma somatomedin levels remained extremely low. Over a period of 2 years of treatment, growth response and loss of subcutaneous fat were minimal. On serial dilution in radioimmunoassay, his growth hormone (GH) molecule yielded a parallel line with the HGH standard. In electrofocusing experiments the GH molecule was in the same H range as growth hormone in acromegalic plasma and the major peak of clinical grade HGH (5·03 against 5·01 and 4·98). It is concluded that an overall and specific diminished responsiveness to HGH is present in this patient. This includes a lack of generation of somatomedin, which is thought to be the cause of his short stature. There was no evidence of abnormality of the GH molecule.
Topics: Adrenal Insufficiency; Blood Protein Disorders; Body Height; Calcium; Child; Creatinine; Growth Disorders; Growth Hormone; Humans; Insulin; Isoelectric Focusing; Male; Phosphorus; Radioimmunoassay; Skinfold Thickness; Somatomedins; Thyroid Function Tests
PubMed: 4830119
DOI: 10.1136/adc.49.4.297 -
Frontiers in Endocrinology 2020Insulin-like growth factor (IGF) 1 exerts a wide range of functions in mammalians participating not only in the control of growth and metabolism, but also in other...
Insulin-like growth factor (IGF) 1 exerts a wide range of functions in mammalians participating not only in the control of growth and metabolism, but also in other actions such as neuroprotection. Nutritional status modifies the IGF system, although little is known regarding how diet affects the newest members of this system including pregnancy-associated plasma protein-A (PAPP-A) and PAPP-A2, proteases that liberate IGF from the IGF-binding proteins (IGFBPs), and stanniocalcins (STCs) that inhibit PAPP-A and PAPP-A2 activity. Here we explored if a 1-week dietary change to either a high-fat diet (HFD) or a low-fat diet (LFD) modifies the central and peripheral IGF systems in both male and female Wistar rats. The circulating IGF system showed sex differences in most of its members at baseline. Males had higher levels of both free ( < 0.001) and total IGF1 ( < 0.001), as well as IGFBP3 ( < 0.001), IGFBP5 ( < 0.001), and insulin ( < 0.01). In contrast, females had higher serum levels of PAPP-A2 ( < 0.05) and IGFBP2 ( < 0.001). The responses to a short-term dietary change were both diet and sex specific. Circulating levels of IGF2 increased in response to LFD intake in females ( < 0.001) and decreased in response to HFD intake in males ( < 0.001). In females, LFD intake also decreased circulating IGFBP2 levels ( < 0.001). In the hypothalamus LFD intake increased IGF2 ( < 0.01) and IGFBP2 mRNA ( < 0.001) levels, as well as the expression of NPY ( < 0.001) and AgRP ( < 0.01), but only in males. In conclusion, short-term LFD intake induced more changes in the peripheral and central IGF system than did short-term HFD intake. Moreover, these changes were sex-specific, with IGF2 and IGFBP2 being more highly affected than the other members of the IGF system. One of the main differences between the commercial LFD employed and the HFD or normal rodent chow is that the LFD has a significantly higher sucrose content, suggesting that this nutrient could be involved in the observed responses.
Topics: Animals; Diet, Fat-Restricted; Diet, High-Fat; Female; Gene Expression Regulation; Male; Rats; Rats, Wistar; Receptors, Somatomedin; Sex Factors; Somatomedins
PubMed: 32849298
DOI: 10.3389/fendo.2020.00513