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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin was modified with d-biotin-N-hydroxysuccinimide ester in dimethylformamide. Mono-, di-, and triacylated insulins were separated by preparative isoelectric focusing. Monoacylated derivatives (isoelectric point 5.1) were fractionated twice on DEAE-cellulose to yield pure N epsilonB29-biotinylinsulin. The structure of the product was established by amino acid analysis before and after deamination. N epsilonB29-biotinylinsulin had biological activity indistinguishable from insulin on glucose oxidation and lipid synthesis assays using isolated rat epididymal fat cells. Complexes of N epsilonB29-biotinylinsulin with avidin, having essentially all but one binding site filled with biotin, were prepared in order to obtain a 1:1 insulin:avidin ration. The elicited identical maximal biological responses, but showed a potency decreased to 5% of that of insulin. Such complexes conjugated with ferritin will provide a useful tool in the development of electron microscopic stains of insulin receptors.
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PMID:N epsilonB29-(+)-biotinylinsulin and its complexes with avidin. Synthesis and biological activity. 62 Nov 98

We investigated the possibility that insulin could stimulate translation of ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line that expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h after exposure to 70 nM insulin, ODC enzyme activity increased approximately 50-fold and mRNA accumulation 3-fold in the HIR 3.5 cells but not in normal fibroblasts. Pretreatment of cells with cycloheximide completely inhibited insulin-stimulated ODC expression; actinomycin D partially inhibited this effect. To determine the influence of the 5' untranslated region (5'UTR) of ODC mRNA on insulin-regulated ODC expression, plasmids were constructed which contained sequences from the 5'UTR of a rat ODC mRNA interposed between the ferritin promoter and the coding region of the human growth hormone gene. These constructions were then expressed transiently in HIR 3.5 cells. Insulin stimulated a 2-4-fold change in growth hormone accumulation in the medium of cells transiently expressing plasmids containing the entire 5'UTR of ODC mRNA or just the 5'-most 115 bases, a G/C-rich conserved sequence predicted to form a stem-loop structure and shown previously to be responsible for constitutive inhibition of translation. There was a direct correlation between the extent of insulin stimulation and the predicted secondary structure of the added 5'UTR sequences. To determine whether this effect might be due to insulin activation of initiation factors responsible for melting mRNA secondary structure, we examined the effect of insulin on the phosphorylation states of two such factors, eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the phosphorylation of both initiation factors; this stimulation was evident at 15 min and maximal by 60 min. These results suggest a potential general mechanism by which insulin could preferentially stimulate translation of mRNAs whose 5'UTRs exhibit significant secondary structure by activating initiation factors involved in melting such secondary structures.
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PMID:Insulin induction of ornithine decarboxylase. Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E. 198 89

Recent data have shown that ferritin, a ubiquitous protein, has a role as a regulator of cellular differentiation. In the present study we have investigated the expression of ferritin mRNAs in cultured C6 cells, a rat glioma cell line, in response to insulin, which has an important role in cellular growth and differentiation. Insulin stimulated steady state levels of both ferritin heavy chain and ferritin light chain mRNAs. An increase in the level of ferritin heavy or light chain mRNA was detected after 2 h of incubation with insulin, and a plateau was reached after 48 h for heavy chain mRNA and after 72 h for light chain mRNA. The responses were dose-dependent and were maximal at 100 nM for both mRNAs. Treatment of cells with actinomycin-D showed that insulin had no effect on the posttranscriptional stability of these mRNAs. Actinomycin-D inhibited insulin-induced accumulation of both mRNAs, suggesting transcriptional stimulation of ferritin genes by insulin. A nuclear run-on assay showed that the insulin-induced increase in ferritin heavy chain mRNA was due to an increase in the rate of gene transcription. We also demonstrated that insulin-like growth factor-I (IGF-I) increased ferritin heavy and light chain mRNA levels in a dose-dependent fashion, and that the maximum effect was obtained at a concentration of 10 nM on both mRNA levels. IGF-I was not only 10-fold more potent, but the absolute level of maximum stimulation was also about 2-fold greater than that for insulin. The combination of insulin (100 nM) and IGF-I (10 nM) showed no additive effect. The results suggested that the ferritin heavy and light chain genes are transcriptionally regulated by insulin and influenced by IGF-I.
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PMID:Transcriptional regulation of ferritin messenger ribonucleic acid levels by insulin in cultured rat glioma cells. 199 66

In order to assess the possible effects of insulin on serum concentrations of trace metals (iron, copper, zinc) and trace metal binding proteins (ferritin, transferrin, coeruloplasmin), five normal females were studied with the hyperinsulinaemic-euglycaemic clamp technique. A 0.1 U/kg insulin bolus was administered, followed by an insulin infusion at a rate of 10 mU/kg/min for 12-16 h. Insulin levels of 1500-2000 microU/ml (9.21-12.28 nmol/l) were attained. When iron levels in serum were assayed colorimetrically, there appeared to be a progressive rise in the mean concentration during the course of the insulin infusion. Direct analysis of serum samples by atomic absorption spectrophotometry also showed that the level of non-haeme iron increased 3-fold in the serum of the subject with the lowest concentration of this metal at the start of the study. In contrast with the results for serum iron, the levels of ferritin, total iron binding capacity (transferrin), zinc, copper and coeruloplasmin were not altered in any subject during the insulin infusion or at 24 h following discontinuation of the infusion. Within 4 h of institution of the hyperinsulinaemic clamp significant reductions in serum levels of potassium, phosphorus, cholesterol, total protein and albumin were noted. As the insulin infusion progressed, the urea nitrogen, uric acid and bicarbonate levels fell as well. These observations suggest that supraphysiologic hyperinsulinaemia of 12-16 h duration may alter serum levels of iron, but not serum levels of zinc, copper or trace metal binding proteins in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of extreme hyperinsulinaemia on serum levels of trace metals, trace metal binding proteins, and electrolytes in normal females. 354 94

Biochemical and ultrastructural studies of insulin binding and cellular processing by cultured H4IIEC3 hepatoma cells were performed. Insulin binding and intracellular accumulation were rapid and after 30 min at 37 degrees C, 65% of the total cell-associated 125I-insulin was in an acid-stable compartment. Chloroquine had no significant effect on the amount of total cell-associated insulin or the percentage of insulin in the acid-stable compartment or cell-associated insulin degradation under those conditions, but after 60-min incubations, it slightly decreased the rate of dissociation of internalized hormone. Ultrastructural analysis revealed that monomeric ferritin-insulin (Fm-I) initially bound to single or paired receptors on microvilli. Within 5 min occupied insulin receptors microaggregated and migrated to the intervillous cell surface. During the next 5-10 min occupied receptors aggregated into large clusters on the plasma membrane. Large amounts of insulin were internalized by macropinocytosis and the majority of internalized Fm-I was found in phagosomes. Less than 10% of the membrane-bound insulin was associated with pinocytotic invaginations or coated pits and less than 5% of the total cell-associated insulin was found in lysosomes. Chloroquine had no detectable effect on the amount of Fm-I or its distribution among the intracellular organelles. These studies demonstrated that, compared to previous studies with rat adipocytes or 3T3-L1 adipocytes, insulin interalization and intracellular processing in this hepatoma cell were unique. These differences provide further evidence that insulin binding and processing may be controlled by cell-specific mechanisms and that substantial heterogeneity exists in pathways previously presumed to be similar for all cell types.
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PMID:Insulin binding and processing by H4IIEC3 hepatoma cells: ultrastructural and biochemical evidence for a unique route of internalization and processing. 354 44

Capillary endothelium can actively regulate vascular permeability of various serum proteins. Hormones such as insulin must interact with this capillary barrier in order to reach their respective target tissues. We have studied the binding and subsequent internalization of 125I-insulin in both native (freshly isolated) and primary cultured capillary endothelium derived from rat epididymal fat pads. Insulin association with the endothelium, internalization and degradation differed between freshly isolated and primary cultured capillaries. Specific binding in freshly isolated and cultured capillaries was temperature dependent, and was competitively inhibited in the presence of unlabelled insulin. Primary cultures of capillaries grown to confluence did not exhibit specific binding of insulin. Despite the lack of specific receptors for insulin, cultured cells vesicularly internalized insulin. Greater than 50% of the total associated insulin was not degraded by cultured endothelium. Morphological examinations using ferritin labelled insulin localized insulin associated to the capillary endothelial cell membrane and sequestered within pinocytotic vesicles. Incubation of freshly isolated capillaries with insulin stimulated the fluid phase endocytosis of 14C-sucrose; however, insulin had no effect on fluid phase endocytosis in cultured capillaries. These results indicate that capillary endothelium, isolated from rat epididymal fat, exhibit specific receptors for insulin. Binding of insulin to the capillary membrane is followed by internalization into cytoplasmic vesicles and partial degradation.
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PMID:Insulin binding and vesicular ingestion in capillary endothelium. 390 93

Monomeric ferritin-insulin and high-resolution electron microscopic analysis were used to study the organization, distribution, and movement of insulin receptors on differentiated 3T3-L1 adipocytes. Analysis of the binding to prefixed cells showed that insulin initially occupied single and paired receptors preferentially located on microvilli. The majority of receptors (60%) were found as single molecules and 30% were pairs. In 1 min at 37% C, 50% of the receptors on nonfixed cells were found on the intervillous plasma membrane and more than 70% of the total receptors had microaggregated. By 30 min only 7% of the receptors were single or paired molecules on microvilli. The majority were on the intervillous membrane, with 95% of those receptors in groups. The receptor groups on the intervillous plasma membrane could be found in both noncoated invaginations and coated pits. The concentration of occupied receptors in the noncoated invaginations and the coated pits was similar; however, ten times more noncoated invaginations than coated pits contained occupied insulin receptors. The observations in this study contrast with those reported on rat adipocytes using identical techniques (Jarett and Smith, 1977). Insulin receptors on adipocytes were initially grouped and randomly distributed over the entire cell surface and did not microaggregate into larger groups. Insulin receptors on rat adipocytes were found in noncoated invaginations but were excluded from the coated pits. The differences in the organization and behavior of the insulin receptor between rat and 3T3-L1 adipocytes suggest that the mechanisms regulating the initial organization of insulin receptors and the aggregation of occupied receptors may be controlled by tissue-specific processes. Since both of these cell types are equally insulin sensitive, the differences in the initial organization and distribution of the insulin receptors on the cell surface may not be related to the sensitivity or biological responsiveness of these cells to insulin but may affect other processes such as receptor regulation and internalization. On the other hand, the microaggregates of occupied receptors on both cell types may relate to biological responsiveness.
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PMID:Ultrastructural analysis of the organization and distribution of insulin receptors on the surface of 3T3-L1 adipocytes: rapid microaggregation and migration of occupied receptors. 392 Feb 28

Ruthenium red binding demonstrates that the extensive microvesicle system of isolated rat adipocytes is, for the most part, open to and continuous with the plasmalemma proper. Morphometric estimates indicate that insulin treatment has no effect on the relationship between microvesicles and the cell surface. Neither does insulin affect the apparent lack of pinocytotic activity of these vesicles as judged by a time course analysis of cells incubated with horseradish peroxidase, which is bound to the membrane of the vesicles, but is not internalized. Insulin does produce a small but repeatable and measurable increase in average diameter of the microvesicles from 73 to 78 nm. Unlike the positively charged ruthenium red, which binds to both plasmalemmal as well as microvesicular surfaces, cationic ferritin did not readily bind to microvesicle membranes, a result indicating some distinction between the two membrane surfaces. The implications of the lack of dramatic visible morphological effects of insulin upon the adipocyte plasmalemma and it's associated microvesicles are discussed in light of the proposed role of insulin as a mediater of translocation of membrane-associated transporters to and from the cytoplasm.
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PMID:The relationship of microvesicles to the plasmalemma of rat adipocytes. 619 5

Glucose intolerance is a common consequence of transfusion therapy in patients with thalassemia major (TM), but the relative contribution of pancreatic damage and insulin resistance to glucose intolerance is unclear. We have investigated oral (OGTT) and intravenous (IVGTT) glucose tolerance, insulin sensitivity, and fasting concentrations of insulin, proinsulin, and des 31,32 proinsulin in 12 patients with TM (seven hepatitis C virus [HCV] antibody-negative and five-positive), eight patients with hepatic cirrhosis, and nine healthy controls. Two-hour plasma glucose concentrations were marginally higher in anti-HCV-negative (median, 7.4 mmol/ L; range, 4.0 to 8.2) and significantly so in anti-HCV-positive thalassemics (median, 8.5 mmol/L; range, 6.4 to to 23.0) and cirrhotics (median, 8.0 mmol/L; range, 4.7 to 17.6) than in controls (median, 5.5 mmol/L; range, 3.0 to 6.3). Insulin sensitivity was also reduced in the three patient groups (P < .05). Insulin resistance was the main determinant of oral glucose intolerance in all patient groups (partial r2 = .49, P < .0001, n = 28). In turn, the main determinants of insulin insensitivity in TM patients were liver damage (albumin, r = .67, P = .02) and serum ferritin concentration (r = -.62, P = .03). There was no relationship of either 2-hour or incremental insulin concentrations with ferritin levels or with HCV status in TM subjects. Moreover, these patients showed no elevation of concentrations of proinsulin and des 31,32 proinsulin, markers of pancreatic beta-cell damage, in excess of those observed in cirrhotic patients. In conclusion, the glucose intolerance of TM, like that of cirrhosis, is associated with insulin resistance, not insulin deficiency, and may be a direct or indirect consequence of hepatic damage.
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PMID:Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction. 862 11

Ten patients (18 +/- 1 yr) on chronic hemodialysis (HD) with anemia were studied before and after treatment with erythropoietin (EPO) for 9 mo. Six patients had evidence of iron overload (serum ferritin over 300 ng/ml; group I) and the other four patients (serum ferritin below 300 ng/ml; group II) did not. Before treatment, both groups of patients were glucose tolerant but insulin resistant and hyperinsulinemic. There was equal correction of anemia but no significant changes in serum biochemistry (apart from iron studies) or anthropometric measurements in both groups. With amelioration of anemia and iron overload in group I, insulin sensitivity increased by 53% to within normal values. Insulin secretion also normalized. With amelioration of anemia but no change in iron status in group II, insulin sensitivity (increased by 60%) and insulin secretion also normalized. Thus correction of anemia by EPO reversed insulin resistance and hyperinsulinemia in HD patients with or without iron overload. The effects of correction of anemia rather than iron overload may be more important in the pathogenesis of insulin abnormalities in end-stage renal disease.
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PMID:Correction of anemia by erythropoietin reverses insulin resistance and hyperinsulinemia in uremia. 892 46


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