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

Hep G2 cells were used to study the early sequence of events regulating production of insulin-like growth factor-binding protein-1 (IGFBP-1). Cytochalasin B (100 microM) specifically inhibited 2-deoxyglucose uptake by Hep G2 cells and stimulated IGFBP-1 production 2-fold. Insulin (300 nM) did not stimulate hexose uptake but inhibited IGFBP-1 production more than 50%. A change in IGFBP-1 secretion was observed as early as 2 h after a 15-min or 2-h pulse exposure to either effector. In contrast to IGFBP-1, albumin production was diminished in the presence of cytochalasin B and increased by insulin. From these results we conclude that IGFBP-1 synthesis is (i) stimulated by transient inhibition of cellular glucose uptake and further stimulated by long-term glucose deprivation, and (ii) inhibited by transient exposure to insulin with further inhibition on long-term exposure. These effects are consistent with the dynamic regulation of IGFBP-1 by nutritional status.
Mol Cell Endocrinol 1991 May
PMID:Cytochalasin B stimulates insulin-like growth factor-binding protein-1 production by Hep G2 cells. 172 53

Insulin has rapid pleiotropic effects on cellular metabolism. In certain cell types, insulin can cause morphological changes by inducing rearrangements of cytoskeletal components, but the regulation of cytoskeletal gene expression by insulin has not been previously described. In the present work insulin was found to rapidly, but transiently, increase transcription of the cytoskeletal beta-actin and alpha-tubulin genes in rat H4IIE hepatoma cells. Insulin-induced transcription of beta-actin mRNA was evident within 5 min and was maximal by 10-15 min at 1000% above control levels. beta-Actin transcription was induced at insulin concentrations as low as 5 x 10(-12) M insulin and was maximal at 5 x 10(-9) M. Transcription of the alpha-tubulin gene was also rapidly stimulated by physiological concentrations of insulin, but only to 300-400% above basal levels. For both the beta-actin and alpha-tubulin genes, the induction of transcription was transient, with a return to basal levels by 60-120 min. Transcription of neither the skeletal or cardiac alpha-actin gene nor the beta-tubulin gene was altered by insulin administration. Messenger RNA levels for the beta-actin and alpha-tubulin genes increased, but to a lesser extent than transcription, since these mRNAs were abundant and stable before the transient induction of transcription. Inhibitors of protein synthesis, in the presence or absence of insulin, also acutely stimulated transcription of these genes.
Mol Endocrinol 1992 Jan
PMID:Induction of cytoskeletal gene expression by insulin. 173 64

The effect of insulin on the production and degradation of 2-deoxyglucose-6-phosphate (2DG6P) from 2-deoxyglucose (2DG) in the Langendorff-perfused rat heart was studied by 31P NMR. The 2DG concentrations ranged from 0.25 to 20 mM in the 5 mM acetate perfusion medium, and from 2 to 4 mM in the 12 mM glucose medium. With acetate as the carbon source, the apparent Km for the production of 2DG6P was 7 mM and Vmax was 1.8 mumols/min/mg prot. Insulin enhanced Vmax 7-fold without change in Km of the transporter. With glucose perfusion, insulin had no effect on the initial rate of production of 2DG6P. The interpretation is that glucose phosphorylation is regulated by work when glucose is the energy substrate. In acetate-perfused hearts, in the conditions where the 2DG6P content reached a plateau, the rate of production of 2DG6P (equal to the measured degradation rate, see below) was eight times smaller than the initial rate, both with and without insulin. In glucose-perfused hearts, it was the same as the initial rate. The degradation of 2DG6P upon interruption of 2DG perfusion was exponential. The time constant was the same in acetate or glucose. It was strongly affected by insulin, being 225 +/- 60 min without, and 92 +/- 13 min with insulin. The observation that 2DG6P degradation is sensitive to insulin in the heart shows that its rate may vary. This possibility should be kept in mind in the analysis of PET studies of glucose metabolism.
J Mol Cell Cardiol 1991 Oct
PMID:Insulin increases the rate of degradation of 2-deoxy-glucose-6-phosphate in the perfused rat heart: a 31P NMR study. 174 2

The insulin-degrading enzyme (IDE) is an evolutionarily conserved enzyme that has been implicated in cellular insulin degradation, but its site of action and importance in regulating insulin degradation have not been clearly established. We addressed this question by examining the effects of overexpressing IDE on insulin degradation in COS cells, using both human IDE (hIDE) and its Drosophila homolog (dIDE). The dIDE, which was recently cloned in our laboratory, has 46% amino acid identity with hIDE, degrades insulin with comparable efficiency, and is readily expressed in mammalian cells. Transient expression of dIDE or hIDE in COS monkey kidney cells led to a 5- to 7-fold increase in the rate of degradation of extracellular insulin, indicating that IDE can regulate cellular insulin degradation. Insulin-degrading activity in the medium was very low and could not account for the difference between transfected and control cells. To further localize the site of IDE action, the fate of insulin after receptor binding was examined. The dIDE-transfected cells displayed increased degradation of prebound insulin compared to control cells. This increase in degradation was observed even when excess unlabeled insulin was added to block reuptake or extracellular degradation. These results indicate that IDE acts at least in part within the cell. The lysosomotropic agents chloroquine and NH4Cl did not affect the increase in insulin degradation produced by transfection with dIDE, indicating that the lysosomal and IDE-mediated pathways of insulin degradation are independent. The results demonstrate that IDE can regulate the degradation of insulin by intact cells via an intracellular pathway.
Mol Endocrinol 1991 Oct
PMID:Regulation of insulin degradation: expression of an evolutionarily conserved insulin-degrading enzyme increases degradation via an intracellular pathway. 177 31

Rat insulin-like growth factor-I (IGF-I) mRNAs with different 5'-untranslated region/prepeptide coding sequences result from transcription initiation in one of two leader exons. While not altering the mature IGF-I coding sequence, these different leaders potentially encode two distinct IGF-I prepeptides, one of 48 amino acids (exon 1) and one of 32 amino acids (exon 2). Within exon 1, transcription initiation is dispersed (i.e. occurs over a approximately 350-basepair region), while within exon 2, it is highly localized. A fourth exon 1 start site, residing only approximately 30 basepairs from its 3' end, is suggested on the basis of RNase protection assays; its use would produce an mRNA encoding a third distinct IGF-I leader peptide of 22 amino acids. We have determined that during postnatal development, and as a result of insulinopenic diabetes and fasting, choice of transcription start sites within exon 1 in the liver is coordinately regulated, i.e. use of all start sites increased during development and decreased in the two catabolic states. Transcription initiation at the single major site within exon 2 was also reduced in diabetes and fasting. Insulin replacement therapy and refeeding restored the levels of all transcripts coordinately. During postnatal development, however, transcripts initiating within exon 2 exhibited a different developmental profile than did exon 1 transcripts, increasing especially at the onset of GH-dependent linear growth. In liver, therefore, negative regulation of exon 1 and exon 2 transcription start site usage occurs in catabolic states, while in development, differential regulation of exon 1 and exon 2 transcription start sites occurs.
Mol Endocrinol 1991 Nov
PMID:Regulation of start site usage in the leader exons of the rat insulin-like growth factor-I gene by development, fasting, and diabetes. 177 70

Diabetes in the rat is associated with poor growth and decreased GH in the pituitary. In this study we have examined whether this reduction reflects an impairment of GH gene expression. Diabetes was induced by the administration of streptozotocin (7 mg/100 g BW), and 18 days later, GH content, GH mRNA, and GH transcription rate were determined. GH mRNA levels were reduced by more than 80% in the pituitaries of diabetic rats, which had a similarly reduced GH content. The differences observed in transcription fully account for the changes in mRNA concentration, since the transcription rate of the gene was also reduced by a factor of 10 in the diabetic pituitaries. Insulin therapy (3 U/15 days) partially restored these parameters. The expression of the specific transcription factor GHF-1/Pit-1 in diabetic rats was also analyzed. Both GHF-1 mRNA levels and the binding of nuclear proteins to an oligodeoxynucleotide conforming to the GHF-1 proximal binding site in the promoter of the GH gene were normal in the diabetic pituitaries, thus excluding the possibility that decreased availability of this factor could be responsible for the decreased GH transcription. Since diabetes produced an approximately 3-fold reduction of circulating T3, the potential role of thyroid hormones on GH gene expression was also evaluated in thyroidectomized and thyroidectomized diabetic rats. Thyroidectomy decreased GH and GH mRNA to less than 5% of the values found in intact animals, and a single saturating injection of T3 (250 micrograms/100 g BW) resulted in a 8- to 10-fold induction of GH mRNA after 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Nov
PMID:Expression of the growth hormone gene and the pituitary-specific transcription factor GHF-1 in diabetic rats. 177 74

Insulin suppresses growth hormone expression and induces prolactin (PRL) biosynthesis in MtT/S cells cultured in a medium supplemented with normal sera. Incorporation of [35S]amino acids into immunoprecipitable PRL became detectable at 15 h of culture with insulin (500 ng/ml) and increased up to 48 h. Northern blot hybridization demonstrated a concurrent induction of PRL mRNA. However, insulin failed to induce PRL in a medium supplemented with steroid-depleted sera. Either pre- or cocultivation of cells with 10 pM to 10 nM 17 beta-estradiol (E2), which did not induce PRL by itself, restored the insulin-mediated PRL biosynthesis in a dose-dependent manner. Diethylstilbestrol was as effective as E2, whereas testosterone, progesterone and corticosterone were without effect. The E2 action was partially suppressed by tamoxifen. These results suggest that estrogen is required for the insulin-mediated induction of PRL biosynthesis in MtT/S cells.
Mol Cell Endocrinol 1991 Dec
PMID:Estrogen-insulin synergism in induction of prolactin in growth hormone-producing cells. 179 11

Studies carried out on the adrenal glands of experimental diabetic rats have shown an important inhibition in polyenoic fatty acid biosynthesis. This effect was demonstrated by testing the activities of long-chain fatty acyl-CoA synthetase, the delta 5- and delta 6-desaturases of the (n-6) essential fatty-acid series and the delta 6-desaturase of the (n-3) series in liver and adrenal microsomes. The depression in desaturating activity in the insulin-deprived animals was independent of that produced on acyl-CoA-thioester biosynthesis. Experiments measuring the incorporation and transformation of [1-14C]eicosa-8,11,14-trienoic acid in adrenocortical cells isolated from streptozotocin-diabetic animals demonstrated a significant inhibition of arachidonic acid biosynthesis compared to controls. Insulin injections in diabetic rats partially restored the delta 5- and delta 6-desaturase activities. This effect could result from direct action by the hormone since the restoration was reproduced when arachidonic acid biosynthesis was measured after insulin was added to the incubation medium of adrenocortical cells isolated from diabetic animals. The results of the present study provide new information about the implication of this abnormal metabolism in the adrenal gland of diabetic rats.
Mol Cell Endocrinol 1991 May
PMID:Abnormal metabolism of polyunsaturated fatty acids in adrenal glands of diabetic rats. 184 41

Quiescent benzo[alpha]pyrene-transformed BALB/c 3T3 fibroblasts (line BP-A31), continue to express 'competence' genes (such as c-myc) and do not require platelet-derived growth factor ('competence' factor) in order to resume the cell division cycle. Insulin-like growth factor I (IGF-I), as well as insulin (at high concentrations, where it interacts with IGF-I-receptors) are potent mitogens in these cells. In contrast with the original non-transformed A31 cell line, we show that insulin/IGF-I (even in the absence of de novo protein synthesis) induce actin transcription in BP-A31 cells. We have verified that 'CArG' boxes, major actin promoter elements, can act as insulin-inducible elements in BP-A31 cells. Insulin-induced actin transcription is also observed in quiescent A31 cells stably transfected with a myc expression vector, suggesting a correlation between constitutive myc expression and insulin-induced actin transcription.
Mol Cell Endocrinol 1991 Mar
PMID:Insulin/insulin-like growth factor I induce actin transcription in mouse fibroblasts expressing constitutively myc gene. 185 Nov 11

Rats and mice retain a duplicated insulin (I) gene. Because the duplicated gene shares only incomplete homology with the ancestral insulin (II) gene it may be regulated differently. In the studies presented here we measured changes in abundance of these distinct insulin mRNAs and their precursors in response to fasting and fasting plus a single dose of cyproheptadine, two experimental manipulations that cause changes in the level of total insulin mRNA in rats. Both diminished rat insulin II mRNA to a greater extent than rat insulin I mRNA. Rat insulin II mRNA comprised 41% of the total insulin mRNA in 0 h controls and decreased to 33% of the total insulin mRNA after a 10-h fast. Insulin II mRNA decreased to 26% of the total insulin mRNA 10 h after treatment with cyproheptadine. To determine whether these manipulations had effects on insulin mRNA synthesis, precursors for each of the two mRNAs were quantified. Fasting for 24 h had only small effects on insulin I mRNA precursor, but diminished rat insulin II pre-mRNA to 32% of the 0 h control values. One and a half hours after fasting plus cyproheptadine administration, pre-mRNA for rat insulin II levels had decreased to 38%, while rat insulin I pre-mRNA remained at levels present in 0 h controls. Levels of rat insulin I and II pre-mRNAs were both maximally depressed at 10 h, but rat insulin II pre-mRNA decreased to 3%, while rat insulin I pre-mRNA diminished to only 49% of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Apr
PMID:Differential regulation of rat insulin I and II messenger RNA synthesis: effects of fasting and cyproheptadine. 192 87


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