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

Results of previous studies indicated that insulin at levels comparable to those in humans during hyperinsulinemia decreased ACTH-stimulated cortisol and androstenedione secretion by bovine adrenal fasciculata-reticularis cells in primary culture. In the present studies this inhibitory action was examined further by comparing the effects of insulin on ACTH-stimulated corticosteroid secretion with its effects on 8-(4-chlorophenylthio)-cAMP (cpt-cAMP), forskolin- and [5val]angiotensin II (Ang II)-stimulated corticosteroid secretion. Effects on corticosteroid secretion were correlated with effects on cAMP accumulation and rates of cAMP production. Monolayers were incubated for 24 h in the absence or presence of each agonist alone or in combination with insulin. Insulin (1.7 x 10(-9) or 17.5 x 10(-9) M) caused about a 50% decrease in cortisol and androstenedione secretion in response to ACTH (10(-11) or 10(-8) M). Insulin also decreased ACTH-stimulated aldosterone secretion by cultured glomerulosa cells. Cpt-cAMP (10(-4) or 10(-3) M)-stimulated increases in cortisol and androstenedione secretion were inhibited by insulin, but to a lesser extent than those in response to ACTH. The inhibition of cpt-cAMP-stimulated steroid secretion was not related to increased degradation of the cyclic nucleotide. Increases in cortisol and androstenedione secretion caused by a submaximal concentration (10(-6) M) of forskolin were decreased 50-70% by insulin. In contrast, insulin failed to significantly affect cortisol or androstenedione secretion caused by a maximal concentration (10(-5) M) of forskolin. The secretory responses to Ang II (10(-8) M) were also unaffected by insulin. The effect of insulin to inhibit ACTH-stimulated steroid secretion was accompanied by a reduction in cAMP accumulation as well as an apparent inhibition of adenylate cyclase activation. These data indicate that the effect of insulin to attenuate ACTH-stimulated corticosteroid secretion results from both an inhibition of ACTH-stimulated adenylate cyclase activity and an antagonism of the intracellular actions of cAMP.
J Steroid Biochem Mol Biol 1992 Jan
PMID:Mechanisms of insulin inhibition of ACTH-stimulated steroid secretion by cultured bovine adrenocortical cells. 137 Sep 6

Insulin-like growth factors I and II (IGF I and II) are polypeptides with both growth-promoting and insulin-like metabolic effects. Immunoreactive IGF I is present in the retina and both IGF I and II are present in vitreal fluid. The type I and type II IGF receptors are also localized within the neural retina. The presence of IGFs and IGF receptors within the eye suggests a possible growth-promoting effect of IGFs on ocular tissues. IGF may enter the eye from the blood or, alternatively, arise from an ocular cell type which synthesizes and secretes IGF. IGF I and II mRNA synthesis in scleral cells and IGF I synthesis in rat retina suggests endogenous IGF production in the eye. We hypothesized that IGFs and IGF receptors are synthesized by one ocular cell type, the retinal pigment-epithelium (RPE). As a first step in studying IGF production by the RPE, we analyzed expression of the IGF and IGF receptor genes by cultured human RPE cells. Using Northern analysis, RNase protection and reverse-transcriptase polymerase chain reaction (RT-PCR), we found that cultured RPE cells synthesize mRNA for IGF I and the type I and type II IGF receptors.
Brain Res Mol Brain Res 1992 Jan
PMID:Gene expression of the insulin-like growth factors and their receptors in cultured human retinal pigment epithelial cells. 137 66

Insulin-like growth factor 1 (IGF-1) regulates growth of the brain. In order to characterize the variant IGF-1 present in human fetal brain we have determined the cDNA sequence for human fetal brain IGF-1. Using PCR to amplify cDNA obtained from isolated human fetal brain mRNA, two cDNA sequences encoding precursor proteins which correspond to IGF-1a and IGF-1b were obtained. This is the first characterisation of IGF-1 and its IGF-1a and IGF-1b precursors in the nervous system.
Brain Res Mol Brain Res 1992 Jan
PMID:Characterization of two cDNAs encoding insulin-like growth factor 1 (IGF-1) in the human fetal brain. 137 70

Several endocrine hormones which influence liver metabolism are known to increase in activity during the acute phase of injury or inflammation. We determined whether these hormones have the potential to influence acute-phase protein production in human and rat hepatoma cells. Catecholamines, glucagon, growth hormone, triiodothyronine, and cyclic nucleotides individually or in combination did not modulate the basal or the interleukin-1 (IL-1)-, IL-6-, and dexamethasone-stimulated levels of acute-phase plasma proteins. Insulin, however, was found to be a rapid, nonspecific, and dose-dependent inhibitor of the cytokine and glucocorticoid stimulation of acute-phase protein gene expression and to exert its effect at the transcriptional level. The insulin inhibition applied to all cytokines tested but to various degrees, depending upon the particular acute-phase gene. Insulin resulted in an early and prominent increase in the transcription of genes encoding the AP-1 components of JunA, JunB, and c-Fos, as has been observed for other growth factors. However, the effect of insulin on C/EBP beta was unexpected and paradoxical: while insulin completely inhibited the transcriptional activation of the C/EBP beta gene in cytokine- and dexamethasone-treated cells, the level of cytoplasmic C/EBP beta RNA was elevated. Quantitation of C/EBP beta mRNA by Northern (RNA) blot analysis and of C/EBP beta DNA binding activity by Southwestern (DNA-protein) blot analysis showed that insulin, when combined with cytokines and dexamethasone, stimulated both the mRNA and DNA binding activity by a factor of 1.6 compared with that of cells treated with cytokines and dexamethasone alone. Transient transfection of H-35 and HepG2 cells with a chloramphenicol acetyltransferase (CAT) gene expression vector containing the C/EBP beta response element also resulted in a 1.5-fold increase of C/EBP beta-mediated transcription in insulin-treated cells. Transfection of CAT gene constructs containing increasing lengths of heptaglobin gene 5' flanking sequences indicated that insulin inhibition of IL-6 stimulation required the presence of the region from -4100 to -1030. These results suggest that insulin has the potential to control the transcription of acute-phase genes by at least two separate mechanisms.
Mol Cell Biol 1992 Apr
PMID:Insulin is a prominent modulator of the cytokine-stimulated expression of acute-phase plasma protein genes. 137 89

Insulin-like growth factors (IGFs) are polypeptide hormones with structural homology to proinsulin. IGFs circulate in blood bound to specific IGF binding proteins (IGFBPs). cDNA sequences of six members of a family of human and rat IGFBPs have been published. Here we present a partial characterization of the human IGFBP-2 gene. This single copy gene is located on chromosome 2 and spans a total of more than 32 kilobases (kb) of genomic sequence. It is organized in four exons with sizes of more than 568, 220, 141, and 496 nucleotides. The intron between exon one and exon two contributes 27 kb to the size of the IGFBP-2 gene. The second and the third introns comprise 1.1 kb and 1.95 kb, respectively. When the structure of the IGFBP-2 gene is compared to that of the IGFBP-1 and IGFBP-3 genes, the exon boundaries are found to be conserved in these three genes. A single transcriptional start site was localized to 113 +/- 2 nucleotides 5' of the ATG start codon of IGFBP-2 translation. Furthermore, the region between nucleotides -635 and -2 upstream of the ATG was demonstrated to exhibit promoter activity in human Jurkat K16 cells. This region is devoid of TATA or CAAT consensus sequence motifs and has a high content of dC and dG nucleotides. In this respect the putative IGFBP-2 promoter region resembles the promoters which are often associated with housekeeping genes.
Mol Endocrinol 1992 May
PMID:Structure of the human insulin-like growth factor binding protein-2 gene. 137 11

This work explored the role of the cholinergic pathway, assessed at a post-synaptic level by the use of isolated smooth muscle cells, in the impairment of antral motility associated with diabetic gastroparesis. Contractile response to carbachol--but not to erythromycin, a motilin receptor agonist--was abolished in antral smooth muscle cells isolated from (i) rats previously rendered diabetic by a single i.v. dose of streptozotocin (STZ, 60 mg/kg) and (ii) db/db spontaneously diabetic mice. Insulin treatment of STZ-rats was able to prevent the impairment of the carbachol contractile response, but not to reverse it once established. In STZ-rats, impairment of contractile response was not associated with a change in density of [3H]-N-methyl-scopolamine ([3H]-NMS) binding sites (approximately 1.5 fmol/mg protein). Displacement curve of the [3H]-NMS binding by carbachol was shifted to the right in diabetic rats as compared to controls. The addition of GTP-gamma-S induced a shift to the right of the displacement curve in control but not in diabetic animals. These results strongly suggest that diabetes is associated with an early and specific alteration of the muscarinic control of contraction of antral smooth muscles at a post-synaptic level, associated with an alteration of the GTP-binding proteins coupled to muscarinic receptors.
Mol Cell Biochem 1992 Feb 12
PMID:Impairment of contractile response to carbachol and muscarinic receptor coupling in gastric antral smooth muscle cells isolated from diabetic streptozotocin-treated rats and db/db mice. 138 42

Insulin-like growth factors (IGFs) are important stimulators of proliferation and differentiation of cultured myoblasts. It has previously been shown that IGF-I is induced during muscle regeneration in rodents, however, little is known about the expression of IGF-II. Therefore, two in vivo models were used to analyze IGF-II mRNA expression during skeletal muscle regeneration in the rat: injection of the snake venom notexin and induction of ischemia. During the regeneration process the levels of both IGF-I and IGF-II mRNA were transiently induced, as analyzed by solution hybridization. Both IGF-I-like immunoreactivity and IGF-II-like immunoreactivity were found to be present during muscle regeneration. In a time course study, induction of IGF-II was preceded by IGF-I, both at the mRNA and protein levels. Using alpha- and beta-actin as markers for different stages of skeletal muscle differentiation, together with the immunohistochemistry data, it is concluded that the expression of IGF-I and IGF-II occurs at different differentiation stages, and that IGF-II appears concomitant to the formation of myotubes. These results suggest that each IGF has a distinct role during the differentiation of muscle cells.
Mol Endocrinol 1992 Aug
PMID:Activation of insulin-like growth factor II expression during skeletal muscle regeneration in the rat: correlation with myotube formation. 140 1

Time course of the surface electrical activity was studied in left ventricular trabeculae of Wistar rats made diabetic using streptozotocin. The action potentials were recorded in Tyrode's solution at 32 degrees C, their duration considerably increased in diabetes. By the 8th week, the prolongation was 64% at 25% of repolarization; 112% at 50% and 118% at 75%. Insulin treatment reduced the prolongation of the action potentials although a complete restoration was not achieved. 0.1 mM La3+ moderately shortened the electrical activity both in control and in diabetic trabeculae. Three mM 4-aminopyridine made the time course of control action potentials very similar to the diabetic ones while the action potentials from the diabetic animals were prolonged further to a smaller extent. Whole-cell clamp experiments in isolated ventricular myocytes (20-23 degrees C) showed a considerable decrease and a somewhat accelerated inactivation of the transient outward current (Ito) in diabetes. The steady-state inactivation and the rate of recovery from inactivation of Ito did not change. No alterations in the magnitude and voltage dependence of inward rectifier (IK1) were found around the resting membrane potential. The diabetes-related suppression of Ito explains the decreased repolarization rate of action potentials.
J Mol Cell Cardiol 1992 Aug
PMID:Action potentials and potassium currents in rat ventricular muscle during experimental diabetes. 143 14

Insulin gene expression has been demonstrated in nonpancreatic tissues early in development, suggesting that this hormone might have actions significant for the differentiating embryo. Because such actions imply ligand-receptor binding, we quantified mRNAs encoding the two known forms of insulin receptor in rat liver and yolk sac, two endodermally derived tissues shown to express insulin genes, between gestation days (E) 13 and E21 (mid-organogenesis to parturition). Because of its presumed importance for fetal growth, we estimated the abundance of mRNA encoding insulin-like growth factor 1 (IGF 1) receptor in the same samples for comparison. The abundance of insulin receptor mRNA exceeded that for IGF 1 receptor mRNA in liver and yolk sac at all times studied. This difference was greater in liver, where insulin receptor mRNAs were three to more than 50 times more abundant than IGF 1 receptor mRNA on gestation days E13-E16, times which antedate the development of significant hepatic metabolic actions of insulin. The marked abundance of mRNAs encoding insulin receptors is consistent with the hypothesis that insulin has significant actions in specific tissues during the organogenic period.
Mol Endocrinol 1992 Oct
PMID:Insulin receptor gene expression during development: developmental regulation of insulin receptor mRNA abundance in embryonic rat liver and yolk sac, developmental regulation of insulin receptor gene splicing, and comparison to abundance of insulin-like growth factor 1 receptor mRNA. 144 16

Vascular endothelium is the dynamic interface in transport of lipid from blood to myocytes in heart and arteries. The luminal surface of endothelium is the site of action of lipoprotein lipase on chylomicrons and VLDL and the site of uptake of fatty acids from albumin. Fatty acids and monoacylglycerols are transported from the lumen in an interfacial continuum of endothelial and myocyte membranes. Lipoprotein lipase is transferred from myocytes to the vascular lumen, and is anchored there, by proteoheparan sulfate in cell membranes. Insulin, needed for synthesis of lipoprotein lipase and esterification of fatty acids, is captured from the blood stream and delivered to myocytes by endothelial insulin receptors. Fatty acids, monoacylglycerols, lipoprotein lipase and insulin are transported along the same route, but by different mechanisms. The route involves the plasma membrane of endothelium and myocytes, the membrane lining transendothelial channels, and intercellular contacts.
Mol Cell Biochem 1992 Oct 21
PMID:Endothelium, the dynamic interface in cardiac lipid transport. 148 Jan 47


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