Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly sulfated, heparinlike species of heparan sulfate proteoglycans, with heparinlike glycosaminoglycan chains, are extracellular matrix components that are plasma membrane bound in growth-arrested liver cells. Heparins were found to inhibit the growth and lower the clonal growth efficiency of HepG2, a minimally deviant, human hepatoma cell line. Heparan sulfates, closely related glycosaminoglycans present in the extracellular matrix around growing liver cells, had no effect on the growth rate or clonal growth efficiency of HepG2 cells. Neither heparins nor heparan sulfates had any effect on the growth rate or clonal growth efficiency of two poorly differentiated, highly metastatic hepatoma cell lines, SK-Hep-1 and PLC/PRF/5. Heparin's inhibition of growth of HepG2 cells correlated with changes in the mRNA synthesis and abundance of insulinlike growth factor II (IGF II) and transforming growth factor beta (TGF beta). HepG2 cells expressed high basal levels of mRNAs encoding IGF II and TGF beta that were inducible, through transcriptional and posttranscriptional mechanisms, to higher levels by specific heparin-hormone combinations. For both IGF II and TGF beta, the regulation was multifactorial. Transcriptionally, IGF II was regulated by the additive effects of insulin, glucagon, and growth hormone in combination with heparin; TGF beta was regulated primarily by the synergistic effects of insulin and growth hormone in combination with heparin. Posttranscriptionally, the mRNA abundance of the IGF II 4.5- and 3.7-kb transcripts was affected by insulin. Heparin induction of all IGF II transcripts was also dependent on triiodotyronine and prolactin, but it is unknown whether their induction by heparin was via transcriptional or posttranscriptional mechanisms. Heparin-insulin combinations regulated TGF beta posttranscriptionally. The poorly differentiated hepatoma cell lines PLC/PRF/5 and SK-Hep-1 either did not express or constitutively expressed low basal levels of IGF I, IGF II, and TGF beta, whose mRNA synthesis and abundance showed no response to any heparin-hormone combination. We discuss the data as evidence that matrix chemistry is a variable determining the expression of autocrine growth factor genes and the biological responses to them.
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PMID:Heparin and hormonal regulation of mRNA synthesis and abundance of autocrine growth factors: relevance to clonal growth of tumors. 184 19

Growth hormone (GH) secretion can presently be investigated by several methods: pharmacological provocative tests, study of 24-h GH secretion, measurement of somatomedin-C (Sm-C)/insulin-like growth factor (IGF) I, and the growth hormone-releasing hormone (GHRH) test. In order to compare the results obtained, these methods were used in 257 children with growth retardation (169 boys, 88 girls). Their height SD was -2.7 +/- 0.2, chronological age 11 3/12 +/- 1 6/12 years, and bone age 8 4/12 +/- 1 4/12 years. Mean growth velocity was 4.5 +/- 1.5 cm/year. One hundred and thirty-eight boys and 80 girls were prepubertal, and 31 boys and 8 girls were pubertal (B2 G2). All children underwent the study of 24-h GH secretion (n = 257) and pharmacological provocative tests (two tests, n = 213; one test n = 44). Sm-C/IGF I was measured in prepubertal children (n = 131), and a GHRH test was carried out (n = 153). In addition, the mean integrated concentration of growth hormone secretion (IC-GH) was assessed in a control group of 23 children and was found to be 5.4 +/- 1.2 ng/ml/min. The IC-GH in the group as a whole was 2.6 ng/ml/min. The mean maximum peak during pharmacological tests varied considerably according to the test used, ranging from 7.8 ng/ml for the arginine test to 17.1 ng/ml for the glucagon and betaxolol test. The maximum peak and the 24-h IC-GH were not significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of pharmacological tests and study of 24-hour growth hormone secretion in the investigation of growth retardation in children: analysis of 257 cases. 191 56

Insulin-like growth factor I (IGF I) is structurally similar to insulin and shares many of its biologic properties. We compared the short-term metabolic effects of recombinant IGF I (100 micrograms [13.3 nmol] per kilogram of body weight) and insulin (0.15 IU [1 nmol] per kilogram) in eight healthy volunteers (four men and four women). The hypoglycemic responses to both hormones were nearly identical in the doses used. The lowest blood glucose levels were reached after 30 minutes: 1.98 +/- 0.44 mmol per liter after IGF I and 1.78 +/- 0.29 after insulin. On a molar basis, IGF I was only 6 percent as potent as insulin in the production of hypoglycemia. Insulin also inhibited lipolysis more effectively than IGF I. Levels of epinephrine, norepinephrine, growth hormone, glucagon, and cortisol responded similarly to both agents. The hypoglycemia produced by IGF I is probably due to the supraphysiologic concentrations of the free peptide that result from its rapid intravenous injection. Fifteen minutes after injection, the serum level of IGF I increased from 144 +/- 38 ng per milliliter at base line to 424 +/- 56, of which 80 percent was free in the plasma (not bound to IGF carrier proteins). The determination of whether any of the short-term metabolic effects of IGF I have any clinical application will require further investigation.
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PMID:Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. 329 85

Isolated adult rat hepatocytes were used to investigate and compare the actions of glucose or amino acids and insulin, glucagon, growth hormone, and dexamethasone on the expression of insulin-like growth factor binding protein (IGFBP) mRNA, or the release of IGFBP and IGF peptides in vitro. Ligand blot analysis of culture medium conditioned for 24 h by monolayers of hepatocytes in the presence of 6.5 mM glucose revealed two species of IGFBPs, an abundant form of 30-32 kDa and a minor species of 22-24 kDa. Western blotting showed that two IGFBPs of 29-30 and 32 kDa were recognized by antiserum against hIGFBP-1, whereas hepatocytes contained a 1.6 kb transcript on Northern blot with a rat IGFBP-1 cDNA. Insulin-like growth factor BP-2 mRNA was not detected in hepatocytes and IGFBP-2 immunoreactive peptide not present in conditioned medium. The release of IGFBP-1, determined by ligand blot, was independent of glucose concentration over the range of 2.7 mM-11.1 mM, but IGFBP-1 mRNA was decreased following incubation with 6.5 mM glucose compared with 2.7 mM glucose. The release of IGFBP-1 by hepatocytes was inhibited by insulin (10 nM-1 microM), as was mRNA abundance. However, these effects of insulin on IGFBP-1 diminished with increasing glucose concentration. Increasing concentrations of total amino acids increased IGFBP-1 release as did dexamethasone (100 pM-100 nM), whereas growth hormone and glucagon were without effect. The release of IGF I was increased by insulin, growth hormone and dexamethasone but was decreased by glucagon and amino acids, whereas changes in glucose concentration had no effect. The results show that isolated adult rat hepatocytes release IGF I and IGFBP-1 under the interactive control of nutrients and hormones involved in metabolic homeostasis.
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PMID:Interactive effects of nutrients and hormones on the expression of insulin-like growth factor binding protein-1 (IGFBP-1) mRNA and peptide, and IGF I release from isolated adult rat hepatocytes. 768 12

The aim of this study was to investigate the role of age in the hormonal response to opiate anaesthetic fentanyl. In 90 patients undergoing aortocoronary bypass, 59.6 +/- 9.2 years mean age, 35-81 age range, prolactin (PRL), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH), human growth hormone (HGH), insulin-like growth factor I (IGF I), glucagon and insulin were measured in venous blood samples drawn from fasting patients immediately before, at 8 h in the morning, and 60 min after the induction of anaesthesia with 30 microg/kg intravenous fentanyl bolus, 30 min after a second 7 microg/kg fentanyl bolus. Results showed a higher 60 min PRL peak in older, >65 years, in respect to younger, < or =50 years, patients (57.6 +/- 23.3 vs. 40.6 +/- 13.8 microg/l, P<0.005), with a significant upward trend with age across the entire age span (r=0.32; P<0.002), while no difference by age was found for the basal concentrations. No differences were found between the respective basal and 60 min concentrations for the other hormones investigated. As expected, differences by age were found for FSH, higher in >65 and in 51-65-year-olds than in younger patients (for the basal values, respectively, P<0.02 and P<0.05); IGF I was lower in >65 in respect to < or =50 (P<0.02) and to 51-65-year-old patients (P<0.05), with a significant negative correlation with age (r=-0.33; P<0.005). The study shows an age related increase of PRL concentrations after fentanyl administration. It may be due to the reduction of the hypothalamic dopaminergic tone with aging. IGF I levels have been confirmed to be inversely correlated with age.
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PMID:Age related prolactin secretion in men after fentanyl anaesthesia. 1476 38

Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.
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PMID:Laron syndrome. First report from Greece. 1700 11

Insulin-degrading enzyme (IDE) is a neutral thiol metalloprotease, which cleaves insulin with high specificity. Additionally, IDE hydrolyzes Abeta, glucagon, IGF I and II, and beta-endorphin. We studied the expression of IDE protein in postmortem brains of patients with schizophrenia and controls because: (1) the gene encoding IDE is located on chromosome 10q23-q25, a gene locus linked to schizophrenia; (2) insulin resistance with brain insulin receptor deficits/receptor dysfunction was reported in schizophrenia; (3) the enzyme cleaves IGF-I and IGF-II which are implicated in the pathophysiology of the disease; and (4) brain gamma-endorphin levels, liberated from beta-endorphin exclusively by IDE, have been reported to be altered in schizophrenia. We counted the number of IDE immunoreactive neurons in the dorsolateral prefrontal cortex, the hypothalamic paraventricular and supraoptic nuclei, and the basal nucleus of Meynert of 14 patients with schizophrenia and 14 matched control cases. Patients had long-term haloperidol treatment. In addition, relative concentrations of IDE protein in the dorsolateral prefrontal cortex were estimated by Western blot analysis. There was a significantly reduced number of IDE expressing neurons and IDE protein content in the left and right dorsolateral prefrontal cortex in schizophrenia compared with controls, but not in other brain areas investigated. Results of our studies on the influence of haloperidol on IDE mRNA expression in SHSY5Y neuroblastoma cells, as well as the effect of long-term treatment with haloperidol on the number of IDE immunoreactive neurons in rat brain, indicate that haloperidol per se, is not responsible for the decreased neuronal expression of the enzyme in schizophrenics. Haloperidol however, might exert some effect on IDE, through changes of the expression levels of its substrates IGF-I and II, insulin and beta-endorphin. Reduced cortical IDE expression might be part of the disturbed insulin signaling cascades found in schizophrenia. Furthermore, it might contribute to the altered metabolism of certain neuropeptides (IGF-I and IGF-II, beta-endorphin), in schizophrenia.
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PMID:Reduced neuronal expression of insulin-degrading enzyme in the dorsolateral prefrontal cortex of patients with haloperidol-treated, chronic schizophrenia. 2187 64