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 studied the growth of 89 patients who were long-term survivors of childhood leukemia and lymphoma. Eight patients with CNS relapse had a greater decrease in height standard deviation score (SDS) after the relapse than 81 patients without CNS relapse (p less than 0.0001). Two patients who received cranial irradiation when they were younger than 2 years of age demonstrated a marked decrease in height SDS more than 3.0 SD. Five patients appeared to have a decline in height SDS before their CNS relapse. There were no apparent changes in the weight of patients with or without CNS relapse. In endocrine studies, all eight patients with CNS relapse failed to show the normal growth hormone (GH) response to arginine, GH-releasing factor, and glucagon-propranolol tests, while spontaneous GH secretion during sleep was normal. Magnetic resonance imaging (MRI) revealed small pituitary glands in seven patients with CNS relapse. These findings suggest that in leukemia and lymphoma patients with CNS relapse, GH secretion is impaired at the hypothalamic level, resulting in a secondary atrophy of the pituitary gland. The MRI together with selected endocrinologic tests may help to clarify the mechanism of growth impairment in such patients. A decline in height SDS in each patient may be a useful marker for predicting a CNS relapse in a child with leukemia or lymphoma.
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PMID:Growth retardation in childhood leukemia and lymphoma. Special reference to patients with CNS relapse. 151 Jan 94

The MT-2, derived from an adult T-cell leukaemia (ATL) cell, the Molt-4F, a human T-cell line, and the Isk, an EB virus-transformed B-cell line, were found to have high-affinity receptors for somatostatin, a cyclic tetradecapeptide that inhibits the release of substances such as growth hormone, TSH, glucagon, insulin, secretin, gastrin and cholecystokinin. The quantity of radioactivity bound varied linearly with the number of cells, and was displaced by non-radioactive somatostatin in a concentration-dependent manner. Specific binding of 125I-somatostatin was time- and temperature-dependent and at 22 degrees reached equilibrium within 120 min. Scatchard analysis demonstrated one class of specific-binding sites on MT-2 cells, Isk cells and Molt-4F cells that had respective densities and dissociation constants of 109 pM and 0.64 nM, 102 pM and 1.1 nM, and 5.8 pM and 0.22 nM.
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PMID:Identification of lymphoid cell lines bearing receptors for somatostatin. 289 85

GH, LH, insulin and glucagon patterns were studied in the peripheral leukocytes of normal subjects (granulocytes and lymphocytes separated on a Ficoll-Hypaque gradient) and leukaemic patients (CML, AML, CLL, and ALL), using a double antibody RIA on whole cells. The uptake of 125I-labelled insulin and GH by these cells was also assessed. The results showed that in leukaemia, particularly CLL, ALL and AML, though not in CML, there was a constant reduction in hormone values, plus depressed GH and insulin uptake. The only exceptions were glucagon and insulin in CML, and LH in CLL, since their concentrations were normal or clearly enhanced. The data are seen as an expression of a membrane receptor block extending to several hormones with structural differences (protein, steroid, T3 and T4), capable of altering the ability of leukaemic cells to respond to ordinary factors modulating their differentiation, functional activity, and the expansion of the corresponding stem cell compartment.
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PMID:[Behavior of the principal protein hormones in normal and leukemic leukocytes]. 630 18

In 19 normal subjects an increase in the number of circulating neutrophils was observed after intramuscular injection of 1 mg glucagon. The response began at the end of the 1st hour following the injection and persisted beyond the 8th hour, with a peak between 2 and 5 hours. No response was obtained in patients with bone marrow aplasia, either primary or associated with acute leukaemia. In 20 patients with chronic primary neutropenia, the degree of response was proportional to the percentage of medullary polymorphonuclears. A comparison between the kinetics of the glucagon-induced granulocyte response and that of the response induced by other neutrophil mobilizing agents suggested that glucagon acts by releasing granulocytes from the bone marrow reserve compartment. The finding that an infusion of dibutyryl cyclic AMP results in granulocyte mobilization suggests that the effects of glucagon are mediated by cAMP at cell level. Since the glucagon response test is harmless and gives rapid and pronounced results, it may be useful in investigation of patients with neutropenia. In addition, the glucagon-induced granulocyte mobilization might improve leucocyte yield in blood donors used for transfusion in agranulocytosis.
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PMID:[Glucagon-induced neutrophil mobilization (author's transl)]. 707 58

We report 34 patients (aged 5-18 years) with acute (n = 26) or chronic (n = 1) leukemia, non-Hodgkin's lymphoma (n = 3) or severe aplastic anemia (n = 4) evaluated for pancreatic beta-cell function 9 months to 10.2 years after autologous (n = 19) or allogeneic (n = 15) BMT. Before BMT, all patients received cytotoxic drugs, combined with total body irradiation (TBI) in 24 cases or thoracoabdominal irradiation (TAI) in 4 children. Patients were investigated for fasting blood glucose (FBG), HbA1C, anti-insulin (IAA) and islet cell antibodies (ICA), first-phase insulin response (FPIR) and insulinemia/glycemia (I/G) ratio on i.v. glucose tolerance test (GTT) and C-peptide response after glucagon 1 mg i.v. Results were compared with those obtained in 21 age- and sex-matched controls. None of the patients or controls had IAA and/or ICA. FBG and HbA1C were normal in all children. In the patients, glycemia on i.v. GTT was similar to controls whereas insulin levels I/G ratio and FPIR were significantly higher in patients than in controls, as well as C-peptide levels. We divided the patients on the basis of the radiotherapy into group I with TBI (n = 18), group II with TAI (n = 4) and group III who were not irradiated (n = 4). The I/G ratio, FPIR on i.v. GTT and C-peptide response were significantly higher in group I compared with the other two groups and controls. The increased insulin and C-peptide levels in our patients with normal glycemia might be interpreted as a state of insulin resistance, more evident in patients who received TBL.
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PMID:Hyperinsulinemia in children and adolescents after bone marrow transplantation. 758 Oct 84

The intestinal hormone, glucagon-like peptide-2 (GLP-2), stimulates growth, survival, and function of the intestinal epithelium through increased crypt cell proliferation, and a long-acting analog has recently been approved to enhance intestinal capacity in patients with short bowel syndrome. The goal of the present study was to determine whether GLP-2-induced crypt cell proliferation requires a full complement of B-cell lymphoma Moloney murine leukemia virus insertion region-1 homolog (Bmi-1), using the Bmi-1(eGFP/+) mouse model in comparison with age- and sex-matched Bmi-1(+/+) littermates. Bmi-1 is a member of the polycomb-repressive complex family that promotes stem cell proliferation and self-renewal and is expressed by both stem cells and transit-amplifying (TA) cells in the crypt. The acute (6 h) and chronic (11 d) proliferative responses to long-acting human (Gly(2))GLP-2 in the crypt TA zone, but not in the active or reserve stem cell zones, were both impaired by Bmi-1 haploinsufficiency. Similarly, GLP-2-induced crypt regeneration after 10-Gy irradiation was reduced in the Bmi-1(eGFP/+) animals. Despite these findings, chronic GLP-2 treatment enhanced overall intestinal growth in the Bmi-1(eGFP/+) mice, as demonstrated by increases in small intestinal weight per body weight and in the length of the crypt-villus axis, in association with decreased apoptosis and an adaptive increase in crypt epithelial cell migration rate. The results of these studies therefore demonstrate that a full complement of Bmi-1 is required for the intestinal proliferative effects of GLP-2 in both the physiological and pathological setting, and mediates, at least in part, the proliferation kinetics of cells in the TA zone.
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PMID:Glucagon-Like Peptide-2 Requires a Full Complement of Bmi-1 for Its Proliferative Effects in the Murine Small Intestine. 2718 77

Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a target of GVHD and that GLP-2-based treatment of acute GVHD restores intestinal homeostasis via an increase of ISCs and PCs without impairing GVL effects. Teduglutide could become a novel combination partner for immunosuppressive GVHD therapy to be tested in clinical trials.
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PMID:Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. 3254 57

Glucagon-like peptide-2 (GLP-2), a key factor in intestinal rehabilitation therapy of short bowel syndrome (SBS), may require cell-to-cell communication to exert its biological functions. However, understanding of the mechanism remains elusive. Here, we report participation of exosomal miR-125a/b in GLP-2 mediated intestinal epithelial cells-myofibroblasts cross-talk in intestinal microenvironment. Methods: The effects of GLP-2 on the proliferation and apoptosis of intestinal epithelial cells in SBS rat models were evaluated. Exosomes were extracted from residual jejunum tissue of GLP-2 or vehicle treated SBS rats using ultracentrifugation method, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting. miRNA sequencing combined with qRT-PCR validation were used to identify differentially expressed miRNAs. miRNAs, which might be involved in proliferation and apoptosis of intestinal epithelial cells, were screened and further verified by miRNA functional experiments. Moreover, the proliferation-promoting and anti-apoptosis effects of GLP-2 on intestinal myofibroblasts, which expressing GLP-2 receptor, and whether GLP-2 could influence the content of miRNAs in the derived exosomes were studied. The downstream pathways were explored by miRNA function recovery experiment, luciferase reporter assay, pull down experiment, knockdown and overexpression of target gene and other experiments based on the bioinformatics prediction of miRNA target gene. Results: GLP-2 significantly promoted intestinal growth, facilitated the proliferation of intestinal crypt epithelial cells and inhibited the apoptosis of intestinal villi epithelial cells in type II SBS rats. GLP-2 significantly down-regulated exosomal miR-125a/b both in residual jejunums derived exosomes and in exosomes secreted by GLP-2R positive cells. Exosomal miR-125a/b was responsible for GLP-2 mediated intestinal epithelial cells proliferation promotion and apoptosis attenuation. miR-125a/b inhibited the proliferation and promotes apoptosis of intestinal epithelial cells by suppressing the myeloid cell leukemia-1 (MCL1). Conclusions: miR-125a/b shuttled by intestinal myofibroblasts derived exosomes regulate the proliferation and apoptosis of intestinal epithelial cells. GLP-2 treatment significantly decreases the level of miR-125a/b in the exosomes of intestinal myofibroblasts. miR-125a/b modulates the proliferation and apoptosis of intestinal epithelial cells by targeting the 3'UTR region of MCL1. Hence, this study indicates a novel mechanism of genetic exchange between cells in intestinal microenvironment.
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PMID:Exosomes-mediated Transfer of miR-125a/b in Cell-to-cell Communication: A Novel Mechanism of Genetic Exchange in the Intestinal Microenvironment. 3268 5