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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Androgen receptors have been found in human larynx and androgens have been supposed to play an important role in promoting the growth of laryngeal carcinomas. The molecular mechanism underlaying this phenomenon is not at all understood. Aim of this work was to investigate the effects of two androgens (testosterone and dihydrotestosterone) on insulin receptor mRNA levels and insulin binding activity as well as on either metabolic or growth-promoting actions of insulin in a human larynx carcinoma cell line (HEp-2). We found that HEp-2 cells express a high affinity insulin receptor. Both androgens significantly increase insulin receptor mRNA levels and insulin receptor number in HEp-2 cells. Insulin action, evaluated either as total glucose utilization or as [3H]thymidine incorporation into DNA, significantly increased in HEp-2 treated with androgens in comparison to control cultures. Altogether, our data allow us to speculate that the increased insulin effectiveness we observed in the larynx carcinoma cell line HEp-2 after androgen treatment might be involved in the regulation of larynx cancer cells growth.
Mol Cell Endocrinol 1992 Jul
PMID:Androgens increase insulin receptor mRNA levels, insulin binding, and insulin responsiveness in HEp-2 larynx carcinoma cells. 151 77

In contrast to previous studies, Parker et al. (Diabetes (1989) 38, 1123) have recently found that isolated rat adipocytes alone were unable to synthesize prostaglandins (PG) and that the PG measured in adipocyte suspensions were due to contaminating non-adipocyte cells. In the present study the capacity of adipocytes to produce PGE2 has further been explored. Preparations of isolated rat adipocytes were extensively washed in order to get rid of contaminating cells. The released PGE2 was measured by radioimmunoassay (RIA) after high-performance liquid chromatography (HPLC) separation. We found that after repetitive washing (up to 20 times) the isolated adipocytes were still able to synthesize PGE2 and this process was fully activatable by epinephrine, which indicates that pure adipocytes, themselves, are able to produce PGE2. However, addition of non-adipocyte material (from the adipose tissue) to 'pure' adipocytes (washed 10 times) enhanced the PGE2 synthesis significantly (P less than 0.001) as compared to 'pure' adipocytes alone. Thus, some kind of synergy exists between adipocytes and non-adipocyte cells in the adipose tissue in respect to PG formation. Some regulatory aspects of PG synthesis in 'pure' adipocytes were also investigated. Phospholipase A2 (2 U/ml) enhanced PGE2 synthesis significantly (119 +/- 21 to 658 +/- 85 pg/10(6) cells, P less than 0.001) without affecting lipolysis (glycerol release). The combined effect of epinephrine (5 microM) and phospholipase A2 (2 U/ml) on PGE2 formation was almost additive. Insulin inhibited the epinephrine-induced PG formation (P less than 0.01) but had no effects on the action induced by phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 May
PMID:Biosynthetic capacity and regulatory aspects of prostaglandin E2 formation in adipocytes. 152 16

MCF-7 cells were grown in serum free medium (Dulbecco MEM without phenol red, supplemented with Costar SF-1 without insulin). Insulin was added as required and gave dose dependent growth stimulation at concentrations between 5 and 10,000 nM. Identical growth response curves were obtained for thymidine uptake and cell number. Oestradiol and insulin-like growth factor I (IGF-I) added individually both gave a dose dependent stimulation of cell growth in serum free medium containing 50 nM insulin. The growth stimulatory effect of oestradiol was to a large extent inhibited with suramine, a general inhibitor of growth factors, indicating that the effect of oestradiol was mediated through stimulating autocrine secretion of a growth factor. To investigate a possible link between the effects of oestradiol and IGF-I, a specific IGF-I receptor antibody (alpha IR-3), 10 micrograms/ml was used. These experiments were carried out with 2.5 nM insulin in the medium, a concentration at which insulin had no growth stimulatory effect. Stimulation was carried out for 18 h before assay of thymidine uptake. The effect of oestradiol was not significantly reduced by alpha IR-3, indicating that IGF-I was not an autocrine mediator of oestradiol stimulation of cell growth under these conditions, whereas alpha IR-3 extensively reduced growth stimulation by IGF-I. On long term stimulation (5 days) oestradiol had a marked stimulatory effect on cell number and alpha IR-3 almost totally abrogated this effect. When oestradiol (1 nM) and IGF-I (2.5 nM) were added together, the combined effect on thymidine incorporation and cell number was significantly greater than additive. This synergistic effect on the IGF-I growth response was totally abolished by the IGF-I receptor antibody. The results suggest a cooperative interaction of oestradiol and IGF-I. It is concluded that growth stimulation of MCF-7 cells by long term treatment with oestradiol may be mediated through autocrine secretion of IGF-I. the effect of short term stimulation of thymidine incorporation suggest that the growth response of oestradiol is more complex, and indicate that a cooperative interaction with IGF-I is involved, which is unrelated to stimulated autocrine secretion.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I. 156 24

Synthetic peptides representing unique sequences in rat proinsulin C-peptide I and II were used to generate highly specific antisera, which, when applied on sections of normal rat pancreas, confirm a homogeneous coexpression of the two C-peptides in all islet beta-cells. Insulin gene expression is induced in the transformed heterogeneous rat islet cell clone, NHI-6F, by transient in vivo passage. During this process a transfected human insulin gene is coactivated with the endogenous nonallelic rat insulin I and II genes. Newly established cultures from NHI-6F insulinomas having a high frequency of insulin-producing cells showed highly differential expression at the cellular level of the three proinsulin C-peptide immunoreactivities, as follows: C-peptide I greater than human C-peptide greater than C-peptide II. The fractions of cells expressing human C-peptide and C-peptide II decreased in time and were absent after more than 50 successive passages, while a C-peptide I-producing population was still present. Double-labeling experiments revealed a heterogeneous distribution of the three different C-peptides. Surprisingly, in the early passages a large fraction of cells would express only a single species of proinsulin-C-peptide immunoreactivity but still at high levels. However, rat C-peptide II and human C-peptide were often colocalized, even in later passages. In situ hybridization studies combined with the immunocytochemical data suggest that the differential expression occurs at the level of transcription.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1992 Feb
PMID:Immature transformed rat islet beta-cells differentially express C-peptides derived from the genes coding for insulin I and II as well as a transfected human insulin gene. 156 72

This work investigates the effect of alloxan-induced short-term diabetes (24 h) on D-3-hydroxybutyrate metabolism at physiological and non-physiological concentrations of the ketone body in the isolated non-working perfused rat heart. Also the effect of insulin (2 mU.ml-1) on D-3-hydroxybutyrate metabolism was investigated in hearts from normal and diabetic rats. The rates of D-3-hydroxybutyrate utilization and oxidation and of acetoacetate production were proportional to D-3-hydroxybutyrate concentration. The utilization of D-3-hydroxybutyrate showed saturation kinetics in hearts from normal and diabetic rats, in the presence and absence of insulin. Acute short-term diabetes augmented D-3-hydroxybutyrate utilization and oxidation at 1.25 and 2.5 mM DL-3-HB, with no significant effect at higher concentrations, but increased acetoacetate production at all investigated concentrations. In hearts from normal rats, insulin enhanced D-3-hydroxybutyrate utilization and oxidation at 2.5, 5, and 10 mM DL-3-HB, but no effect was observed at the lowest (1.25 mM) and highest (16 mM) DL-3-HB concentrations. Insulin had no effect on D-3-hydroxybutyrate metabolism in hearts from diabetic rats. No significant effect of insulin on the rate of acetoacetate production in normal and diabetic states was observed.
Mol Cell Biochem 1992 Mar 04
PMID:Effects of diabetes and insulin on ketone bodies metabolism in heart. 157 30

Glucose transporter isoform expression was studied in the skeletal muscle-like cell line, C2C12. Northern and Western blot analysis showed that the insulin-responsive muscle/fat glucose transporter isoform, GLUT 4, was expressed in these cells at very low levels, whereas the erythrocyte isoform, GLUT 1, was expressed at readily detectable levels. Insulin did not stimulate glucose transport in this cultured muscle cell line. The C2C12 cells were then transfected separately with either GLUT 1 or GLUT 4, and stable cell lines expressing high levels of mRNA and protein were isolated. GLUT 1-transfected cells exhibited a 3-fold increase in the amount of the GLUT 1 transporter protein which was accompanied by a 2- to 3-fold increase in the glucose uptake rate. However, despite at least a 10-fold increase in GLUT 4 mRNA and protein detected after GLUT 4 cDNA transfection, the glucose uptake of these cells was unchanged and remained insulin-insensitive. By laser confocal immunofluorescence imaging, it was established that the transfected GLUT 4 protein was localized almost entirely in cytoplasmic compartments. In contrast, the GLUT 1 isoform was detected both at the plasma membrane as well as in intracellular compartments. These results suggest that acute insulin stimulation of glucose transport is not solely dependent on the presence of the insulin receptor and the GLUT 4 protein, and that the presence of some additional protein(s) must be required.
Mol Endocrinol 1992 Mar
PMID:Expression of the glucose transporter isoform GLUT 4 is insufficient to confer insulin-regulatable hexose uptake to cultured muscle cells. 158 10

To investigate the role of Ca2+ metabolism and pH in diabetic cardiomyopathy, intracellular Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) of isolated myocytes were measured simultaneously using fura-2 and BCECF. We used diabetic (D.M.) rats at 8 weeks after the injection of streptozotocin (45 mg/kg, i.v.). (1) [Ca2+]i of D.M. myocytes was lower than that of controls (53 +/- 3 and 75 +/- 5 nM, mean +/- S.E., P less than 0.01). There was no difference in pHi (7.06 +/- 0.02 in D. M., 7.07 +/- 0.02 in control). There was no difference in the percentage of non-rounded cells at 30 min after the perfusion of glucose-free solution which contained 2 mM sodium cyanide (NaCN) between D.M. and controls (53% and 52%). When cells were rounded, the value of [Ca2+]i was significantly lower in D.M. myocytes than that in controls (172 +/- 21 and 421 +/- 106 nM, P less than 0.05). (2) When the cells were shortened or rounded in the high [Ca2+]o solution (24.5 mM), [Ca2+]i of D.M. rats was significantly lower than that of control rats. (3) The percentage of non-rounded cells at 30 min after the perfusion of NaCN increased in controls by 50 mM glucose (95%, P less than 0.01), but not in D.M. (47%). Insulin (25 mU/ml) and glucose (15 mM) increased the percentage of non-rounded cells in D.M. after 30 min perfusion with NaCN (88%, P less than 0.01 v.s. 53% without glucose nor insulin). It is suggested that there are disturbances of Ca2+ metabolism in D.M. myocytes, and that there is a close relation between cell injury and glucose utilization during metabolic inhibition.
J Mol Cell Cardiol 1992 Apr
PMID:Cytosolic Ca2+ concentration and pH of diabetic rat myocytes during metabolic inhibition. 161 71

In ongoing studies aimed at elucidating the mechanism of insulin action on the expression of genes that modulate glucose utilization and cell growth, we have focused on the inductive effect of insulin on transcription of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the early growth response gene, Egr-1. Insulin acutely stimulates the expression of both genes in 3T3 adipocytes; however, in primary adipocytes, chronic insulin exposure has opposing effects on the expression of these genes. GAPDH mRNA is decreased in the epididymal fat cells of diabetic animals and is increased over control levels when insulin is replaced, while Egr-1 mRNA levels are increased in diabetic animals. These observations, coupled with the finding that insulin-stimulated Egr-1 gene transcription is impaired in a Chinese hamster ovarian (CHO) cell line that displays normal metabolic responses but impaired ability to regulate DNA synthesis, support the conclusion that insulin regulation of Egr-1, a growth response gene, and GAPDH, a metabolic response gene, are mediated by distinct pathways. We present evidence that supports the role of protein phosphorylation in mediating the effect of insulin on activation of Egr-1 and GAPDH gene transcription.
Mol Cell Biochem 1992 Feb 12
PMID:Models of insulin action on metabolic and growth response genes. 162 85

Replicative DNA synthesis, as measured by thymidine incorporation, has been measured in rat uterine cells in primary culture in response to growth factors. Insulin, insulin-like growth factor-I (IGF-I), multiplication-stimulating activity (MSA) and platelet-derived growth factor (PDGF) stimulated DNA synthesis, while estradiol, epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF) and relaxin did not stimulate or did so weakly and only at very high concentrations. Uterine acid extracts also stimulated DNA synthesis. IGF-I stimulated at concentrations consistent with its acting through the IGF-I receptor; however, insulin stimulated at concentrations higher than expected for its acting through its receptor and this its action may be mediated through the IGF-I receptor. IGF-I was found in uterine tissue by radioimmunoassay (RIA). There was a 5- to 10-fold increase in IGF-I in the uteri from ovariectomized rats that had been treated with estradiol 24 h earlier. This is analogous to the increase in growth factor activity found previously in rat uterus after 24-h estradiol treatment (Beck, C.A. and Garner, C.W. (1989) Mol. Cell. Endocrinol. 63, 93-101). These data are consistent with the hypothesis that estradiol effects in the uterus are in part mediated through IGF-I.
Mol Cell Endocrinol 1992 Mar
PMID:Stimulation of DNA synthesis in rat uterine cells by growth factors and uterine extracts. 163 15

Insulin stimulates transcription and cytoplasmic accumulation of a specific mRNA (termed p33), while inhibiting transcription and accumulation of phosphoenolpyruvate carboxykinase (PEPCK) mRNA in rat H4IIE (H4) hepatoma cells. The present work examines the role of protein synthesis in regulation of these genes by insulin and dexamethasone. Like insulin, cycloheximide and anisomycin, two protein synthesis inhibitors, induced p33 transcription and reduced PEPCK transcription. The combination of either protein synthesis inhibitor and insulin did not induce p33 transcription or inhibit PEPCK transcription beyond that observed with either protein synthesis inhibitor alone. Dexamethasone induced both p33 and PEPCK transcription. The combination of insulin and dexamethasone, or protein synthesis inhibitors and dexamethasone, abolished dexamethasone-induced PEPCK transcription. Thus, protein synthesis inhibitors regulate transcription of the p33 and the PEPCK genes in an insulin-like manner.
Mol Cell Endocrinol 1992 Mar
PMID:Protein synthesis and insulin regulation of p33 and PEPCK gene expression. 163 18


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