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)

Primary cultures of ovine ruminal epithelial cells were made to study the influence of collagen types I and IV out of medium supplementation with various hormones and Na-n-butyrate on cell morphology and growth characteristics. Both collagen type I and type IV led to increased cell proliferation with the stimulatory effect being more pronounced in collagen IV. In cultures grown on collagen I, both non-stratified and stratified colonies were found, whereas cultures grown on collagen IV showed predominantly stratified growth. Cells in both stratified and non-stratified colonies were positive for cytokeratin antibody. In non-stratified colonies, positive staining with fibronectin antibodies (FN-15) was found in a network over and around the cells. It is suggested that the non-stratified ruminal epithelial cells are in some respects similar to a 'non-differentiating keratinocyte' strain, derived from newborn foreskin epidermis. Cells in stratified colonies bound Ulex europaeus (UEAI) lectin which has been shown to be specific for differentiated epithelial cells in ruminal mucosa. Supplementation of culture medium with glucagon and insulin increased the total cell-overgrown area of collagen I cultures, whereas this effect was absent in cultures grown on collagen IV. In both cultures grown on collagen I or IV, hydrocortisone led to an increase in total cell-overgrown area, whereas Na-n-butyrate inhibited proliferation.
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PMID:Influences of extracellular matrix components on the growth and differentiation of ruminal epithelial cells in primary culture. 843 37

We have previously described the use of a chemically defined medium (CDM) supplemented with epidermal growth factor (EGF) and dimethylsulfoxide (DMSO) to maintain long-term cultures of rat hepatocytes in a highly differentiated state. In this study, conditions necessary to stimulate high levels of DNA synthesis in hepatocytes in long-term DMSO culture were defined. Hepatocytes were maintained in culture for 20 days in CDM containing DMSO and EGF, insulin, and glucagon. EGF, insulin, and glucagon were then removed for 7 days. Readdition of EGF, insulin, and glucagon at day 27 (shiftup) was accompanied by a three- to sixfold increase in labeling index. If DMSO or dexamethasone (dex) + DMSO were removed at time of shiftup, the labeling index increased by 18- to 54-fold. TGF beta inhibited DNA synthesis stimulated by EGF shiftup, TGF alpha shiftup, or EGF shiftup in combination with removal of dex + DMSO. Stimulation of DNA synthesis was accompanied by a specific, sequential induction of protooncogene mRNA levels; c-fos mRNA was induced 23-fold at 0.5 h after readdition of EGF; c-myc mRNA was induced three- to four-fold by 0.5 h; TGF alpha mRNA was induced sevenfold by 8 h; K-ras mRNA was induced fourfold by 26 h. Changes in protooncogene expression paralleled changes seen in regenerating liver. When DMSO was removed for greater than 48 h, the cells flattened and spread out, chords of cells were no longer well defined, albumin mRNA levels decreased, and fibronectin, beta 1 integrin, and TGF beta transcripts increased.
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PMID:Stimulation of DNA synthesis and protooncogene expression in primary rat hepatocytes in long-term DMSO culture. 843 3

A three-dimensional (3-D) model of both subunits of interleukin 12 (IL-12) has been created through molecular modeling. Initial assignment of coordinates in the model of the p40 subunit was based on established amino acid sequence homology between the second and third domains of p40 and the human growth hormone receptor (GHR) and new observations of similarity between the first domain of p40 and the N-terminal domain of CD4. Human growth hormone (GH) served as the reference protein for the p35 chain. Furthermore, thorough analysis of the amino acid sequence of IL-12 revealed two distinct regions of the p40 subunit that display homology with other proteins. The first region (in domain two) contains the sequence RGD, which is found in adhesion proteins (such as fibronectin), and the nearby sequence VTCG, which occurs in a diverse set of molecules, Including thrombospondin, properdin, and circumsporozoite proteins of Plasmodium. The second region of homology spans the third domain of p40 and shows marked similarity with the gastrointestinal peptides, such as secretin and glucagon and their preprohormones. We conclude (1) that the regions of homology define functionally important segments of p40 that are fully exposed at the protein surface, and (2) that the third domain of p40 (and its equivalent in the cytokine receptor family) is derived from the same ancestral genes as the gastrointestinal peptides.
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PMID:Molecular model of interleukin 12 that highlights amino acid sequence homologies with adhesion domains and gastrointestinal peptides. 890 42

The metabolic response to trauma and sepsis involves an increased loss of body proteins. Specific sites of changes of protein and amino acid metabolism have been identified. In skeletal muscle, the rate of proteolysis is accelerated greatly. The rate of protein synthesis also may be increased but not enough to match the increase in degradation. Intramuscular glutamine concentration is decreased because of increased efflux and possibly decreased de novo synthesis. In the liver, the rate of synthesis of selected proteins (i.e., albumin, transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased, whereas acute phase protein synthesis is accelerated. Tissues characterized by rapidly replicating cells, such as enterocytes, immune cells, granulation tissue, and keratinocytes, exhibit early alterations in the case of decreased protein synthesis capacity. In these tissues, glutamine use is accelerated. Increased stress hormone (cortisol and glucagon) and cytokine secretion, as well as intracellular glutamine depletion, are potential mediators of altered protein metabolism in trauma and sepsis. However, the relative importance of these factors has not been clarified. Therapy of acute protein catabolism may include the use of biosynthetic human growth hormone, possibly in combination with insulin-like growth factor-1, and the administration of metabolites at pharmacologic doses. We recently studied the effects of carnitine and alanyl-glutamine administration in severely traumatized patients. We found that both carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without affecting selected indices of protein metabolism in the skeletal muscle.
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PMID:Metabolic response to injury and sepsis: changes in protein metabolism. 929 Jan 10

We investigated the effect of various neuropeptides present in the prostate, including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of PC-3 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of tumor cells, whereas SP inhibited it. On the other hand, VIP, CT, L-ENK, NPY, glucagon and PTH-rP had no significant effect. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. These results indicate that both GRP and CGRP increased the invasive potential of PC-3 cells probably through enhancement of cell motility, while SP inhibited the invasiveness through suppression of motile response.
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PMID:Effect of prostatic neuropeptides on invasion and migration of PC-3 prostate cancer cells. 992 57

Extracellular factors that regulate the growth and differentiation of cell lineages in the pancreatic primordia are poorly understood. Identification of these factors for pancreatic islet beta-cells could open new avenues for the treatment of insulin-dependent diabetes. We developed a low cell density serum-free culture system for dissociated pancreatic cells from the 13.5-day mouse fetus and investigated the effects of extracellular matrix proteins on differentiation of islet cells. After 4 days in culture, total cell number decreased by two-thirds, but insulin-positive beta-cell number increased 10-fold. Both of collagens I and IV inhibited cell survival (by >50%), whereas fibronectin had no effect. In the presence of soluble laminin-1, however, the number of beta-cells increased linearly by 60-fold without an increase in the total cell number; glucagon-positive cell number was unchanged, and somatostatin and pancreatic polypeptide-positive cells were not detected. The effect of laminin-1 was completely blocked by a monoclonal rat anti-laminin-1 antibody. In the presence of laminin-1, the thymidine analogue, BrdU, was incorporated into only 2.5% of cells, which were mainly insulin-negative at days 1-3. Laminin-1 appeared, therefore, to induce differentiation of beta-cells from precursor cells in day-13.5 fetal pancreas. Laminin-1 was shown to be expressed in the epithelial basement membrane of the 13.5- to 17.5-day fetal pancreas. These findings provide the first evidence of a role for laminin-1 to promote differentiation of pancreatic beta-cells.
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PMID:Laminin-1 promotes differentiation of fetal mouse pancreatic beta-cells. 1010 87

Few studies have tried to characterize the efficacy of parenteral support of critically ill infants during short period of intensive care. We studied seventeen infants during five days of total parenteral hyperalimentation. Subsequently, according to the clinical conditions, the patients received nutritional support by parenteral, enteral route or both up to the 10th day. Evaluations were performed on the 1st, 5th, and 10th days. These included: clinical data (food intake and anthropometric measurements), haematological data (lymphocyte count), biochemical tests (albumin, transferrin, fibronectin, prealbumin, retinol-binding protein) and hormone assays (cortisol, insulin, glucagon). Anthropometric measurements revealed no significant difference between the first and second evaluations. Serum albumin and transferrin did not change significantly, but mean values of fibronectin (8.9 to 16 mg/dL), prealbumin (7.7 to 18 mg/dL), and retinol-binding protein (2.4 to 3. 7 mg/dL) increased significantly (p < 0.05) from the 1st to the 10th day. The hormonal study showed no difference for insulin, glucagon, and cortisol when the three evaluations were compared. The mean value of the glucose/insulin ratio was of 25.7 in the 1st day and 15. 5 in the 5th day, revealing a transitory supression of this hormone. Cortisol showed values above normal in the beginning of the study. We conclude that the anthropometric parameters were not useful due to the short time of the study; serum proteins, fibronectin, prealbumin, and retinol-binding protein were very sensitive indicators of nutritional status, and an elevated glucose/insulin ratio, associated with a slight tendency for increased cortisol levels suggest hypercatabolic state. The critically ill patient can benefit from an early metabolic support.
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PMID:Nutritional follow-up of critically ill infants receiving short term parenteral nutrition. 1088 Oct 72

To enhance the liver-specific functions of rat hepatocyte aggregates without the addition of exogenous growth factors, polylactic acid-polyglycolic acid (PLGA)/gelatin microcapsules that release insulin, dexamethasone, epidermal growth factors, and glucagon were prepared and incorporated into the hepatocyte aggregates in suspension culture. Precoating the capsules with fibronectin enhanced the incorporation of the microcapsules into the hepatocyte aggregates. In a growth factor- and hormone-free culture medium, these microcapsule-containing aggregates showed a sustained cell number and an ammonium detoxification capacity compared with two types of control culture. One was the culture of microcapsule-free aggregates with albumin-containing control capsules and the other was the culture of capsule-free aggregates that were supplied with the same factors and hormones from the culture medium at concentration levels expected from the release kinetics of the microcapsules. Our new methodology demonstrates that the performance and duration of bioartificial liver systems can be enhanced due to a more efficient maintenance of cell number by using such growth factor- and hormone-releasing microcapsules.
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PMID:In vitro organization of biohybrid rat liver tissue incorporating growth factor- and hormone-releasing biodegradable polymer microcapsules. 1154 75

Type I diabetes mellitus is caused by an autoimmune destruction of the insulin-producing beta cells. The major obstacle in using transplantation for curing the disease is the limited source of insulin-producing cells. The isolation of human embryonic stem (hES) cells introduced a new prospect for obtaining a sufficient number of beta cells for transplantation. We present here a method for forming immature islet-like clusters of insulin-producing cells derived from hES cells. The protocol consisted of several steps. Embryoid bodies were first cultured and plated in insulin-transferrin-selenium-fibronectin medium, followed by medium supplemented with N2, B27, and basic fibroblast growth factor (bFGF). Next, the glucose concentration in the medium was lowered, bFGF was withdrawn, and nicotinamide was added. Dissociating the cells and growing them in suspension resulted in the formation of clusters which exhibited higher insulin secretion and had longer durability than cells grown as monolayers. Reverse transcription-polymerase chain reaction detected an enhanced expression of pancreatic genes in the differentiated cells. Immunofluorescence and in situ hybridization analyses revealed a high percentage of insulin-expressing cells in the clusters. In addition to insulin, most cells also coexpressed glucagon or somatostatin, indicating a similarity to immature pancreatic cells. Further improvement of this insulin-producing cell protocol may lead to the formation of an unlimited source of cells suitable for transplantation.
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PMID:Differentiation of human embryonic stem cells into insulin-producing clusters. 1515 4

Hepatic oval cells (OC) are considered to be facultative liver stem cells and, because they may undergo differentiation into a variety of cell lineages, they might have the potential to be used in cellular therapy. Signals delivered by extracellular matrix (ECM) proteins take part in cellular differentiation in cooperation with signals from growth factors; indeed, some ECM proteins, such as laminin (LAM) and fibronectin (FN), have been shown to contribute to beta-cell differentiation and islet development, respectively. Since no previous studies have investigated the effect of ECM proteins on the expression of islet cell markers by cultured OC, the purpose of the present study was to evaluate whether FN and LAM modulate the expression of genes related to the endocrine pancreas in these liver cells. OC proliferation was induced in Wistar rats by prolonged treatment with 2-acetoaminofluorene/allyl alcohol and confirmed by reverse transcription/polymerase chain reaction and hepatic immunocytochemical and histopathological analyses. OC isolation was performed by Ficoll gradient and magnetic-activated cell sorting. OC were cultured for 1 and 2 months under several conditions with specific growth factors, over a FN or LAM substrate or in high glucose, nicotinamide and fetal calf serum. OC cultured on FN substrate expressed Pdx-1, Pax-6, insulin 2 and glucagon. LAM also induced the expression of Pdx-1, insulin 1 and insulin 2, glucagon, somatostatin and GLUT-2. Our results suggest that these ECM proteins can be used in protocols of OC transdifferentiation aimed at reducing the period necessary for complete transdifferentiation.
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PMID:Fibronectin and laminin induce expression of islet cell markers in hepatic oval cells in culture. 1714 94


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