Insulin pretreatment (imprinting) produces elevated capacity in the insulin binding of Tetrahymena. Different binding by the cilia of the body and oral field

1994 ◽  
Vol 14 (6) ◽  
pp. 301-308 ◽  
Author(s):  
A. K. Fülöp ◽  
G. Csaba
Keyword(s):  
Binding Capacity ◽  
Insulin Binding ◽  
Primary Treatment ◽  
The Body ◽  
Functional Difference ◽  
Hormonal Imprinting ◽  
Pinocytotic Vesicles ◽  
Food Vacuoles

Gold-labeled insulin is bound first of all to the cilia of the oral field of Tetrahymena. A primary treatment (hormonal imprinting) with insulin increases the binding capacity even after 24h and makes it more sensitive for appearance a week later, within a minute of giving insulin-gold. The food vacuoles contain insulin-gold in pretreated cells or without pretreatment as well, though in imprinted situations the label can be found in pinocytotic vesicles at the bases of cilia in the oral field. Altogether, a functional difference can be observed between the cilia of the oral and non-oral surfaces of Tetrahymena and hormonal imprinting has a specifying effect on the binding of labeled hormone.

Bone Manifestation of Faulty Perinatal Hormonal Imprinting: A Review

2019 ◽  
Vol 15 (1) ◽  
pp. 4-9
Author(s):  
G. Csaba
Keyword(s):  
Animal Behavior ◽  
Binding Capacity ◽  
Animal Experiments ◽  
Osteoporotic Fractures ◽  
Postnatal Period ◽  
Hormonal Imprinting ◽  
Adult Age ◽  
Pathological Development ◽  
Synthetic Hormones ◽  
Critical Developmental Period

Hormonal imprinting takes place at the first encounter between the developing receptor and its target hormone and the encounter determines the receptor's binding capacity for life. In the critical period of development, when the window for imprinting is open, the receptor can be misdirected by related hormones, synthetic hormones, and industrial or communal endocrine disruptors which cause faulty hormonal imprinting with life-long consequences. Considering these facts, the hormonal imprinting is a functional teratogen provoking alterations in the perinatal (early postnatal) period. One single encounter with a low dose of the imprinter in the critical developmental period is enough for the formation of faulty imprinting, which is manifested later, in adult age. This has been justified in the immune system, in sexuality, in animal behavior and brain neurotransmitters etc. by animal experiments and human observations. This review points to the faulty hormonal imprinting in the case of bones (skeleton), by single or repeated treatments. The imprinting is an epigenetic alteration which is inherited to the progeny generations. From clinical aspect, the faulty imprinting can have a role in the pathological development of the bones as well, as in the risk of osteoporotic fractures, etc.

scholarly journals Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD. Results HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes. Conclusion HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

Insulin and central regulation of spontaneous fattening and weight loss

1985 ◽  
Vol 249 (2) ◽  
pp. R203-R208
Author(s):  
R. B. Melnyk ◽  
J. M. Martin
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
Binding Capacity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Strong Positive Correlation ◽  
Central Regulation ◽  
Isolated Pancreatic Islets

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.

scholarly journals High glucose and insulin in combination cause insulin receptor substrate-1 and -2 depletion and protein kinase B desensitisation in primary cultured rat adipocytes: possible implications for insulin resistance in type 2 diabetes

2003 ◽  
Vol 148 (1) ◽  
pp. 157-167 ◽  
Author(s):  
J Buren ◽  
HX Liu ◽  
J Lauritz ◽  
JW Eriksson
Keyword(s):  
Glucose Uptake ◽  
High Glucose ◽  
Insulin Treatment ◽  
Insulin Signalling ◽  
Binding Capacity ◽  
Insulin Binding ◽  
Rat Adipocytes ◽  
Glucose Levels ◽  
High Insulin ◽  
The Right

OBJECTIVE: The purpose of this study was to investigate the cellular effects of long-term exposure to high insulin and glucose levels on glucose transport and insulin signalling proteins. DESIGN AND METHODS: Rat adipocytes were cultured for 24 h in different glucose concentrations with 10(4) microU/ml of insulin or without insulin. After washing, (125)I-insulin binding, basal and acutely insulin-stimulated d-[(14)C]glucose uptake, and insulin signalling proteins and glucose transporter 4 (GLUT4) were assessed. RESULTS: High glucose (15 and 25 mmol/l) for 24 h induced a decrease in basal and insulin-stimulated glucose uptake compared with control cells incubated in low glucose (5 or 10 mmol/l). Twenty-four hours of insulin treatment decreased insulin binding capacity by approximately 40%, and shifted the dose-response curve for insulin's acute effect on glucose uptake 2- to 3-fold to the right. Twenty-four hours of insulin treatment reduced basal and insulin-stimulated glucose uptake only in the presence of high glucose (by approximately 30-50%). At high glucose, insulin receptor substrate-1 (IRS-1) expression was downregulated by approximately 20-50%, whereas IRS-2 was strongly upregulated by glucose levels of 10 mmol/l or more (by 100-400%). Insulin treatment amplified the suppression of IRS-1 when combined with high glucose and also IRS-2 expression was almost abolished. Twenty-four hours of treatment with high glucose or insulin, alone or in combination, shifted the dose-response curve for insulin's effect to acutely phosphorylate protein kinase B (PKB) to the right. Fifteen mmol/l glucose increased GLUT4 in cellular membranes (by approximately 140%) compared with 5 mmol/l but this was prevented by a high insulin concentration. CONCLUSIONS: Long-term exposure to high glucose per se decreases IRS-1 but increases IRS-2 content in rat adipocytes and it impairs glucose transport capacity. Treatment with high insulin downregulates insulin binding capacity and, when combined with high glucose, it produces a marked depletion of IRS-1 and -2 content together with an impaired sensitivity to insulin stimulation of PKB activity. These mechanisms may potentially contribute to insulin resistance in type 2 diabetes.

scholarly journals Influence of low- and high-protein diets on insulin and insulin-like growth factor-1 binding to skeletal muscle and liver in the growing rat

1991 ◽  
Vol 65 (1) ◽  
pp. 47-60 ◽  
Author(s):  
D. Dardevet ◽  
M. Manin ◽  
M. Balage ◽  
C. Sornet ◽  
J. Grizard
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Dietary Protein ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
Insulin Binding ◽  
Metabolic Adaptation ◽  
Scatchard Analysis ◽  
Insulin Like Growth Factor ◽  
Hormone Binding

The influence of protein content of the diet on the plasma concentrations and binding to skeletal muscle and liver of insulin and insulin-like growth factor-1 (IGF-1), was studied in growing rats. Animals with a starting body-weight of 80 g received for an 11 d period isoenergetic diets containing (g/kg dry matter) 155 protein as controls (MP), or 55 (LP) or 300 (HP) protein. Food was offered as six equal meals/d. Daily food intakes provided adequate amounts of energy. Total plasma IGF-1 increased linearly as a function of dietary protein intake. Plasma insulin was lower in the LP than in the MP and HP groups. Hormone binding was studied in wheat-germ agglutinin (WGA) partially purified skeletal muscle receptor preparations. Each 125I-labelled hormone binding was competed for by increasing amounts of homologous and heterologous unlabelled hormone; this displacement needed lower concentrations of homologous than heterologous hormone. When compared with MP-diet feeding, the LP diet resulted in an increased ligand concentration for half-maximal binding. In addition the specific 125I-labelled insulin and 125I-labelled IGF-1 binding increased at all hormone concentrations and, as revealed by Scatchard analysis, the hormone binding capacity also rose (only significant for low-affinity insulin receptors and high-affinity IGF-1 receptors). The HP diet had little effect on hormone binding, except to increase insulin binding at very low insulin concentrations. Hormone binding was further studied in WGA partially purified liver receptor preparations. Those preparations did not exhibit any detectable specific 125I-labelled IGF-1 binding. The specific 125I-labelled insulin binding was not altered by dietary protein level. It is concluded that the increase in skeletal muscle insulin and IGF-1 binding along with a decrease in insulin and IGF-1 in the blood from rats fed on the LP diet, is consistent with the concept of an inverse relationship between plasma hormone and hormone binding. The physiological significance with respect to metabolic adaptation of muscle remains to be established

scholarly journals A betegség és a szociodemográfiai háttér hatása a cerebralis bénulásban szenvedő gyermekek életminőségére

2021 ◽  
Vol 162 (7) ◽  
pp. 269-279
Author(s):  
Melinda Fejes ◽  
Beatrix Varga ◽  
Katalin Hollódy
Keyword(s):  
Quality Of Life ◽  
Family Environment ◽  
Negative Impact ◽  
The Body ◽  
Life Questionnaire ◽  
Functional Difference ◽  
Healthy Children ◽  
Related Quality ◽  
Health Related

Összefoglaló. Bevezetés: A kutatócsoport 99 fő, cerebralis paresisben (CP) szenvedő gyermek (8–18 éves) önállóan közölt életminőségét értékelte, és az eredményeket összehasonlította egy 237 fős kontrollcsoport adataival, amelyek hasonló életkorú, egészséges általános populációhoz tartozó gyermekektől származtak. Célkitűzés: A kutatás célja annak megismerése volt, hogy a CP-ben szenvedő gyermekek hogyan vélekednek egészségi állapotukról és társadalmi helyzetükről. Módszer: Életminőség-kérdőív alkalmazása. Betegségspecifikus és társadalmi-demográfiai mutatók mérése, kiértékelése. Eredmények: Az CP-ben szenvedő gyermekek és szüleik az egészséggel kapcsolatos életminőséget rosszabbnak ítélték meg, mint társaik. Eredményeink azt mutatják, hogy a női nem, a rosszabb motoros funkció és a komorbiditások (epilepszia, incontinentia és intellektuális károsodás) negatív hatású. A szülői vélemény alkalmas volt proxyjelentésként a korreláció mért erőssége miatt. Figyelemre méltó, hogy az agyi bénulás típusai közül az egyoldali spasticus CP-ben szenvedő gyermekek életminőség-értéke a legalacsonyabb. A válaszadók valószínűleg a test két oldala között lévő funkcionális különbséget érezték. A szellemi fogyatékosság a betegpopuláció több mint felénél fordult elő. Testvéreik között a mentális betegség 5,7-szer gyakoribb. A CP-s gyerekek családi környezete sokkal hátrányosabb volt, mint az egészséges gyermekeké. A kutatás eredményei alapján megállapítható, hogy a szülő alacsonyabb iskolai végzettsége és munkaerőpiaci inaktivitása, valamint az egyszülős család a CP-s gyerekeknél szignifikánsan magasabb arányban fordult elő, és ezek a tényezők negatív hatást gyakoroltak az életminőségre. Következtetés: A fogyatékkal élő gyermekek életminőségét a betegség és a szociodemográfiai környezet egyaránt befolyásolja. Orv Hetil. 2021; 162(7): 269–279. Summary. Introduction: Self-reported health-related quality of life (HRQoL) of 99 children (8–18 years) with cerebral palsy (CP) was assessed and compared with 237, age-matched healthy control children from the general population. Objective: The aim was to find out the opinions of children with CP about their health status and social condition. Method: Assessment of quality of life questionnaire was carried out. Measurements of disease-specific and sociodemographic variables were done. Results: Children with CP and their parents rated HRQoL poorer than their counterparts. Our results show that female sex, worse gross motor function and comorbidities (epilepsy, incontinence and intellectual impairment) had negative impact. The parental opinion was suitable as proxy report because of the measured strength of the correlation. Among the types of CP, interestingly, children with unilateral spastic CP had the poorest HRQoL. They were likely to feel a functional difference between the two sides of the body. Intellectual disability occurred in more than half of our patient population. Among their siblings, mental illness is 5.7 times more common. The family environment was much more disadvantageous than in the case of healthy children. As our study shows, lower education, inactive status in the labour market and single-parent family occurred at a much higher rate and worsened the quality of life. Conclusion: Quality of life of children with disability was influenced by both the sociodemographic background and the disease. Orv Hetil. 2021; 162(7): 269–279.

Failure of chronic experimental hyperinsulinism to alter insulin binding to hypothalamic receptors in the rat

1984 ◽  
Vol 107 (1) ◽  
pp. 86-90 ◽  
Author(s):  
Roman B. Melnyk ◽  
J. M. Martin
Keyword(s):  
Food Restriction ◽  
Insulin Treatment ◽  
Binding Capacity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Insulin Concentration ◽  
Regulatory Mechanisms ◽  
Hypothalamic Region ◽  
Insulin Levels ◽  
Lateral Area

Abstract. We have previously shown that [125I]insulin binding to medial hypothalamic receptors is attenuated following 14 days of food restriction. Such rats are characterized by considerably reduced circulating insulin levels with unchanged hypothalamic insulin concentration. The present data demonstrate that, in contrast to the effects of starvation, [125I]insulin binding to hypothalamic receptors from rats made hyperinsulinaemic by daily injections of protamine zinc insulin (4–6 U/rat/day for 14 days) is unaffected by this manipulation, even though hypothalamic insulin concentration in insulininjected animals was significantly higher than in salineinjected controls. Insulin binding to partially purified membranes from the medial hypothalamic region was significantly greater than that from the lateral area, confirming a finding in our earlier study. Insulin treatment was associated with slight reductions in maximal insulin-binding capacity of medial hypothalamic receptors, a tendency which appeared to be compensated by reciprocal changes in receptor affinity for this hormone. The data indicate that hypothalamic insulin receptors are not regulated by peripheral or even central insulin levels per se; it appears, rather, that some other, as yet unidentified, correlate(s) of significantly altered food intake and/or body weight can modify hypothalamic insulin receptor function. Perhaps such modifications could, in turn, participate in the activation of regulatory mechanisms involved in correcting energy imbalance.

Roles of interstitial fluid pH and weak organic acids in development and amelioration of insulin resistance

2021 ◽  
Author(s):  
Yoshinori Marunaka
Keyword(s):  
Insulin Resistance ◽  
Organic Acids ◽  
Binding Affinity ◽  
Interstitial Fluid ◽  
Ph Value ◽  
Insulin Binding ◽  
The Body ◽  
Weak Organic Acids ◽  
Arterial Blood ◽  
Blood Ph

Type 2 diabetes mellitus (T2DM) is one of the most common lifestyle-related diseases (metabolic disorders) due to hyperphagia and/or hypokinesia. Hyperglycemia is the most well-known symptom occurring in T2DM patients. Insulin resistance is also one of the most important symptoms, however, it is still unclear how insulin resistance develops in T2DM. Detailed understanding of the pathogenesis primarily causing insulin resistance is essential for developing new therapies for T2DM. Insulin receptors are located at the plasma membrane of the insulin-targeted cells such as myocytes, adipocytes, etc., and insulin binds to the extracellular site of its receptor facing the interstitial fluid. Thus, changes in interstitial fluid microenvironments, specially pH, affect the insulin-binding affinity to its receptor. The most well-known clinical condition regarding pH is systemic acidosis (arterial blood pH < 7.35) frequently observed in severe T2DM associated with insulin resistance. Because the insulin-binding site of its receptor faces the interstitial fluid, we should recognize the interstitial fluid pH value, one of the most important factors influencing the insulin-binding affinity. It is notable that the interstitial fluid pH is unstable compared with the arterial blood pH even under conditions that the arterial blood pH stays within the normal range, 7.35–7.45. This review article introduces molecular mechanisms on unstable interstitial fluid pH value influencing the insulin action via changes in insulin-binding affinity and ameliorating actions of weak organic acids on insulin resistance via their characteristics as bases after absorption into the body even with sour taste at the tongue.

Insulin Binding Sites Induced in the Tetrahymena by Rat Liver Receptor Antibody

1984 ◽  
Vol 39 (1-2) ◽  
pp. 183-185 ◽  
Author(s):  
G. Csaba ◽  
P. Kovács ◽  
Ágnes Inczefi-Gonda
Keyword(s):  
Rat Liver ◽  
Concanavalin A ◽  
Binding Sites ◽  
Binding Capacity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Receptor Antibody ◽  
Receptor Antibodies

Abstract Tetrahvmena cells treated with purified rabbit anti­ bodies to rat hepatocellular membrane exhibited a consider­ able increase in binding capacity on reexposure to the antibody 24 h later. Insulin binding was similarly enhanced by preexposure to the antibody, and vice versa, preex­ posure to insulin enhanced the later binding of rat liver receptor antibodies. This suggests that (1) the Tetrahymena and the rat possess similar insulin receptors, and (2) the receptor antibody is also able to induce imprinting for itself as well as for insulin. Concanavalin-A, noted for binding overlap with insulin, failed to induce imprinting either for insulin or for antibodies to receptors, whereas the latter did induce imprinting for Concanavalin-A.

Interaction Between Genotypes for HFE and TFR2 Genes Mutations and Iron Status in Brazilian Blood Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5382-5382
Author(s):  
Rodolfo D Cancado ◽  
Paulo CJL Santos ◽  
Samuel Rostelato ◽  
Cristiane T Terada ◽  
Iris Gonzales ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Serum Iron ◽  
Blood Donors ◽  
Binding Capacity ◽  
Iron Status ◽  
Hereditary Hemochromatosis ◽  
Transferrin Saturation ◽  
The Body ◽  
Hfe Gene ◽  
Automation System

Abstract Hereditary hemochromatosis (HH) is a disorder characterized by increased intestinal iron absorption, which leads to a progressive accumulation of iron in the body. This iron overload has been associated with mutations in HFE gene (C282Y, H63D and S65C) and other genes. The objectives of this study were to assess the frequencies of functional mutations in HFE and TFR2 genes and to investigate their relationship with the iron status in a sample of blood donors. Blood donors (n=542) were recruited at the Hemocenter of the Santa Casa Hospital, Sao Paulo, Brazil. The genotypes for HFE (C282Y, H63D and S65C) TFR2 (Y250X and Q690P) gene mutations were evaluated by PCR-RFLP. The concentrations of serum iron and total iron-binding capacity (TIBC) were measured by automation system Advia®(Bayer Diagnostics) and serum ferritin by Axsym System®(Abbott Laboratories). The frequencies of HFE 282Y, HFE 63D and HFE 65C alleles were 2.1, 13.6 and 0.6%, respectively. The frequency C282Y allele (2.1%) in Brazilian blood donors is lower than that observed in blood donors from Northern Europe (5.1 to 8.2%, P<0.05). The TFR2 250X and TFR2 690P alleles were not found in these subjects. The iron status was similar between HFE genotypes in women. However, men carrying HFE 282CY genotype had higher serum ferritin and lower TIBC concentrations when compared to the HFE 282CC genotype carriers. HFE 282CY genotype was also associated with higher transferrin saturation in men who donated blood at the first time. Moreover, male donors with HFE 63DD plus 63HD genotypes had higher serum iron and transferrin saturation when compared to those with HFE 63HH genotype. A relationship between HFE CY/HH/SS haplotype and lower TIBC concentrations was also found in men. The HFE 282Y and HFE 65C alleles were rare while the HFE 63D was frequent in blood donors. The mutations in TFR2 gene were not found in this study. The HFE 282Y and HFE 63D alleles were associated with alterations on iron status only in male blood donors.

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