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)

We have developed a radioimmunoassay for human insulin receptor. Serum from a patient with Type B severe insulin resistance was used as anti-insulin receptor antiserum. Pure human placental insulin receptor was used as reference preparation and 125I labeled pure insulin receptor as trace. The radioimmunoassay was sensitive (limit of detection less than 17 fmol), reproducible (inter and intra-assay coefficients of variation 12.5% and 1.6% respectively) and specific (no crossreactivity with pure placental IGF-1 receptor, insulin and glucagon). The anti-insulin receptor antibody was, however, able to differentiate between insulin receptor from human placenta and from rat liver. To determine the number of insulin binding sites per receptor, we measured insulin binding (by insulin binding assay) and insulin receptor mass (by radioimmunoassay) in solubilized aliquots from 5 human placentas. The molar ratio of insulin binding to receptor mass was 0.86 +/- 0.12 when binding was determined with monoiodinated 125I-Tyr A 14-insulin. It was 1.94 +/- 0.27 when randomly iodinated 125I-insulin was used. In conclusion, using a sensitive, reproducible and specific radioimmunoassay, we have measured insulin receptor mass independent of insulin binding. Our data are most compatible with binding of one insulin molecule per human placental insulin receptor.
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PMID:A radioimmunoassay for human insulin receptor correlation between insulin binding and receptor mass. 165 Jul 49

In guinea pigs between days 41-46 of pregnancy prenatal growth has been manipulated by alteration of nutritional state. Three methods were used. Uterine artery ligation at day 30 of pregnancy depressed fetal growth rate by greater than 50% and was associated with falls in plasma insulin, IGF-1, cortisol, thyroid hormone, glucose, acetate and free fatty acid concentrations and rises in that of IGF-2, glucagon and amino acids. Fetal plasma was inhibitory to sulphate incorporation into pig costal cartilage. Complete food withdrawal from pregnant guinea pigs for 2 days at days 43-44 of pregnancy caused mild fetal growth retardation and similar changes in plasma constituents, except in that plasma IGF-2 concentrations were now depressed and plasma was not inhibitory to sulphate incorporation into pig costal cartilage. Production of hypoglycaemia by 4-times-daily maternal injections of glucose between days 41-46 of pregnancy accelerated fetal growth rate. It also elevated fetal plasma concentrations of insulin, IGF-1, IGF-2, sulphation-promoting activity, thyroid hormones, glucose and free fatty acids and depressed that of glucagon and amino acids. Fetal growth rate during the experimental period showed a good correlation with plasma glucose, insulin and IGF-1 and, to a certain extent, with sulphation-promoting activity. It did not correlate closely with fetal plasma IGF-2 concentration. Hepatic glycogen concentrations showed a good correlation with plasma IGF-2 levels.
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PMID:Studies on the growth of the fetal guinea pig. The effects of nutritional manipulation on prenatal growth and plasma somatomedin activity and insulin-like growth factor concentrations. 227 83

Tumor growth in a 72-year-old male patient with malignant haemangiopericytoma in the left hemithorax could be followed radiologically for 4 years before symptoms of recurrent hypoglycaemia appeared. The endogenous insulin level in serum was maximally and serum IGF-1 and IGF-2 markedly reduced. An intravenous arginine load test showed a normal stimulation capacity of the pancreatic glucagon secretion but not that of insulin. After resection of the tumor, blood sugar metabolism was completely normalised. The insulin level, IGF-1 and IGF-2 in serum returned to normal.
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PMID:[Successful therapy of recurrent hypoglycemias by surgical removal of a malignant hemangiopericytoma]. 401 89

Evidence for the presence of peptides, related to insulin-like growth factor 2 (IGF-2), has been obtained in the endocrine pancreas of the elasmobranchian species Raja clavata, the sting ray. By radioimmunoassay, IGF-2-like immunoreactivity was detected in Raja pancreas extract. Further characterization of this activity by acid gel chromatography revealed two distinct peaks of IGF-2-like immunoreactivity with apparent molecular weights of approximately 8.2 kDa and 4.5 kDa. Using the same IGF-2 antibody as well as antisera specific for mammalian IGF-1, insulin, glucagon, somatostatin and pancreatic polypeptide in double immunofluorescence studies, IGF-2-like immunoreactivity was located exclusively in insulin-immunoreactive cells. In contrast, IGF-1-like immunoreactivity was mainly observed in somatostatin- and glucagon-immunoreactive cells. A varying proportion (0-70%) of insulin-immunoreactive cells, however, displayed both IGF-1- and IGF-2-like immunoreactivity. Absorption studies indicated that the IGF-2-like peptides in Raja are different from mammalian and submammalian insulin and mammalian IGF-1, but similar to mammalian IGF-2. Thus, IGF-2-like peptides seem to occur during evolution as early as the phylogenetic development of the elasmobranchians. Furthermore, the results indicate a particularly conservative evolution of the islet IGF-2 system.
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PMID:IGF-2-like peptides are present in insulin cells of the elasmobranchian endocrine pancreas: an immunohistochemical and chromatographic study. 753 39

The carbohydrate-deficient glycoprotein (CDG) syndrome type 1 is a genetic multisystem disorder, characterized by hypoglycosylation of glycoproteins and presenting with neurologic impairment. In 12 girls and 14 boys, we confirmed the diagnosis of CDG syndrome type 1 by immune-isoelectric focusing of serum sialotransferrins, and we examined the endocrine status singly or sequentially, including a 16-y follow-up of the index cases, a pair of monozygotic girls. Serum FSH levels were normal in newborns and prepubertal children, but elevated in female toddlers and teenagers, as well as in adolescent males. Serum LH concentrations displayed an analogous age-dependent pattern. In adolescent girls, serum estradiol remained low. FSH bioactivity was low normal, as was the bioactive/immunoreactive FSH ratio. However, exogenous gonadotropins evoked an estradiol response and induced ovarian follicular growth. Male patients virilized at puberty; however, testicular volume was subnormal. The thyroid axis was hallmarked by thyroid-binding globin deficiency and, during infancy, increased serum TSH concentrations. A subgroup of female patients presented hypersomatotropism and/or hyperprolactinemia. During adolescence, the index cases responded to glucagon with normal glycemic, but exaggerated insulin and paradoxically augmented growth hormone responses. The hypothalamo-pituitary area appeared intact on magnetic resonance imaging. Circulating IGF-1 levels were in the lower normal range and transcortin concentrations decreased. In conclusion, a study of endocrine aspects of a major glycosylation disorder revealed an age-dependent constellation, including hypergonadotropic hypogonadism with deficient FSH rather than LH action; transient hyperthyrotropinemia; inconsistent hyperprolactinemia; hyperglycemia-induced growth hormone release; deficiencies of hormone-binding glycoproteins and possibly decreased insulin sensitivity, thus pointing to the importance of glycoprotein glycosylation for pediatric endocrinology.
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PMID:Endocrinology of the carbohydrate-deficient glycoprotein syndrome type 1 from birth through adolescence. 759 77

Streptozotocin diabetes prevents induction of pancreatic tumors in several animal models, suggesting a pivotal role for islet cell products in the pathogenesis of pancreatic cancer. To test the hypothesis that altered gastrointestinal peptide levels in streptozotocin diabetes influence tumor growth, human pancreatic cancer cells (MIA PaCa-2) were implanted subcutaneously into streptozotocin diabetic nude mice. After 3 weeks, tumors in the control group weighed 43 mg and tumors in the diabetic group weighed 12 mg (P < 0.001). Plasma insulin and IGF-1 levels were significantly decreased in the streptozotocin-treated animals compared to those of control (insulin: 23 microU/ml vs 31 microU/ml, P < 0.001; IGF-1: 254 ng/ml vs 324 ng/ml, P < 0.001). In contrast, somatostatin and glucagon were significantly elevated in the streptozotocin diabetic group relative to control levels (somatostatin: 179 pg/ml vs 54 pg/ml, P < 0.001; glucagon: 290 pg/ml vs 134 pg/ml, P < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd = 15.5 nM), IGF-1 (Kd = 30.0 nM), and somatostatin (Kd = 2.5 nM) on the MIA PaCa-2 cells. Receptors for glucagon were absent. In an in vitro cell proliferation assay, cell division was promoted by insulin (P < 0.01, max + 11%) and IGF-1 (P < 0.01, max + 10%). Somatostatin inhibited cell division (P < 0.01, max - 18%). No effect was seen with glucagon. The growth of pancreatic cancer, particularly in diabetes, may be influenced by gut peptides in a receptor-dependent fashion.
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PMID:GI hormonal changes in diabetes influence pancreatic cancer growth. 779 56

When the supply of energetic substrates is insufficient to slow the development of the catabolism, the next step is to focus on the neuro-endocrine mechanism which regulates the anabolism-catabolism balance. In this work, we review the endocrine response to stress and its implications in protein metabolism, in order to evaluate the different therapeutic possibilities available. Pharmacological blocking of the secretion of catabolic hormones (glucagon and catecholamines) has been unsuccessful up to now. Insulin is the only hormone which produces anabolism in all energetic substrates, but the results published about its administration with glucose and amino acids and its effects upon the nitrogen balance are controversial. The administration of anabolic steroids such as nandrolone, stanolone, and methenolone are usually associated with protein anabolism with minimum androgenizing action. The most recent works lead to the study of the effects of the use of GH and IGF-1 with clearly hopeful results. We have not yet acquired enough experience to use these methods in the habitual clinical practice. At the moment, the clinical studies are in the experimental stage and their application in nutrition is not accepted by the official authorities.
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PMID:[The outlook for hormonal therapy in nutrition]. 798 52

A sensitive RNAse protection method was used to show that serine protease inhibitor-1 (Spi-1) is expressed in rat liver and heart, but not in kidney or brain. Bovine somatotropin (bGH) and placental lactogen (bPL) induced rat hepatocyte cultures to express both Spi-1 and IGF-1 mRNA, with bPL approximately 100-fold more potent than bGH. Bovine prolactin (bPrL) did not induce hepatocyte Spi-1 mRNA, demonstrating lack of involvement of lactogenic receptors. Albumin mRNA levels were stable during hepatocyte culturing and were unaffected by growth hormone (GH) treatment, showing that neither culture conditions nor GH treatment affected cellular differentiation. Eliminating serum-free medium hormone supplements one at a time, estradiol, testosterone and T3 were shown to be unnecessary for GH induction of Spi-1, while dexamethasone removal decreased Spi-1 mRNA levels to 10% of GH-stimulated controls. bGH induction of Spi-1 mRNA in the presence of only dexamethasone and glucagon was 75% higher (p < 0.01) than levels seen with insulin also present.
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PMID:Spi-1: an hepatic serine protease inhibitor regulated by GH and other hormones. 814 11

Development of a high capacity multiplex reverse transcriptase-polymerase chain reaction protocol has allowed us to screen lineage related rat islet tumors classified as alpha-, beta-, and delta-like as judged by their hormone profile for differential expression of more than 50 selected genes. We find that in addition to insulin the insulinoma express the normal beta-cell markers Pdx-1, IAPP, and Glut-2, and that these markers are absent from the glucagonoma: a reflection of the normal alpha-cell. Furthermore, this study suggests that the GLP-1, glucagon, GIP, IGF-1, and insulin receptors as well as E-cadherin, R-cadherin, Id-1, and Id-2 are differentially expressed within the islet of Langerhans. Importantly, insulinoma-specific expression of the recently cloned homeodomain protein Nkx 6.1 predicted beta-cell-specific expression in the normal islet. Immunohistochemistry using antibodies raised against recombinant Nkx 6.1 did indeed localize Nkx 6.1 expression exclusively to the nuclei of normal islet beta-cells. Apart from pancreatic islets only the antral part of the stomach contained Nkx 6.1 mRNA. We conclude that multiplex reverse transcriptase-polymerase chain reaction-based mRNA profiling is a powerful tool to identify differentially expressed genes within phenotypically related cells and propose that Nkx 6.1 is involved in specifying the unique characteristics of the beta-cell.
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PMID:mRNA profiling of rat islet tumors reveals nkx 6.1 as a beta-cell-specific homeodomain transcription factor. 870 31

An anabolic stimulus is needed in addition to conventional nutritional support in the catabolic "flow" phase of severe trauma. One promising therapy appears to be rhGH infusion which has direct as well as hormonal mediated substrate effects. We investigated on a whole-body level, the basic metabolic effects of trauma within 48-60 h after injury in 20 severely injured (injury severity score [ISS] = 31 +/- 2), highly catabolic (N loss = 19 +/- 2 g/d), hypermetabolic (resting energy expenditure [REE] = 141 +/- 5% basal energy expenditure [BEE]), adult (age 46 +/- 5 y) multiple-trauma victims, before starting nutrition therapy and its modification after 1 wk of rhGH supplementation with TPN (1.1 x REE calories, 250 mg N.kg-1.d-1). Group H (n = 10) randomly received at 8:00 a.m. on a daily basis rhGH (0.15 mg.kg-1.d-1) and Group C (n = 10) received the vehicle of infusion. Protein metabolism (turnover, synthesis and breakdown rates, and N balance); glucose kinetics (production, oxidation, and recycling); lipid metabolism, (lipolysis and fat oxidation rates), daily metabolic and fuel substrate oxidation rate (indirect calorimetry); and plasma levels of hormones, substrates, and amino acids were quantified. In group H compared to group C: N balance is less negative (-41 +/- 18 vs -121 +/- 19 mg N.kg-1.d-1, P = 0.001); whole body protein synthesis rate is 28 +/- 2% (P = 0.05) higher; protein synthesis efficiency is higher (62 +/- 2% vs 48 +/- 3%, P = 0.010); plasma glucose level is significantly elevated (256 +/- 25 vs 202 +/- 17 mg/dL, P = 0.05) without affecting hepatic glucose output (1.51 +/- 0.20 vs 1.56 +/- 0.6 mg N.kg-1.min-1), glucose oxidation and recycling rates; significantly enhanced rate of lipolysis (P = 0.006) and free fatty acid reesterification (P = 0.05); significantly elevated plasma levels of anabolic GH, IGF-1, IGFBP-3, and insulin; trauma induced counter-regulatory hormone (cortisol, glucagon, catecholamines) levels are not altered; trauma induced hypoaminoacidemia is normalized (P < 0.05) and 3-methylhistidine excretion is significantly low (P < 0.001). Improved plasma IGF-1 levels in Group H compared with Group C account for protein anabolic effects of adjuvant rhGH and may be helpful in promoting tissue repair and early recovery. Skeletal muscle protein is spared by rhGH resulting in the stimulation of visceral protein breakdown. The hyperglycemic, hyperinsulinemia observed during rhGH supplementation may be due to defective nonoxidative glucose disposal, as well as inhibition of glucose transport activity into tissue cells. The simultaneous operation of increased lipolytic and reesterification processes may allow the adipocyte to respond rapidly to changes in peripheral metabolic fuel requirements during injury. This integral approach helps us to better understand the mechanism of the metabolic effects of rhGH.
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PMID:Integrated nutritional, hormonal, and metabolic effects of recombinant human growth hormone (rhGH) supplementation in trauma patients. 897 4


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