Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor (IR) gene and of the corresponding domain of the rat IR gene results in the synthesis of two IR isoforms with distinct functional characteristics. Altered expression of these IR isoforms has been previously demonstrated in the skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM); however, this observation was not confirmed by other studies and is still a matter of debate. To assess whether the reported altered isoform expression is due to the secondary metabolic derangement of diabetes, we examined alternative splicing of IR mRNAs (IR36+ and IR36-, corresponding to human Ex11+ and Ex11-) in the skeletal muscle and liver of 6-hour fasting 90% pancreatectomized insulin-resistant diabetic and control Sprague-Dawley rats, using the reverse transcriptase-polymerase chain reaction (PCR) technique. Both diabetic and control rats showed the same pattern of IR mRNA expression: the liver exclusively expressed IR36+ mRNA, whereas only IR36- mRNA was detected in muscle. In conclusion, diabetes mellitus per se does not alter the expression of IR isoforms in the liver and skeletal muscle, and therefore, at least in this animal model of NIDDM, impaired insulin action develops independently from a relative increase in IR36+ mRNA expression in skeletal muscle.
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PMID:Expression of the two insulin receptor isoforms is not altered in the skeletal muscle and liver of diabetic rats. 947 57

Genetic susceptibility to type 1 diabetes in the nonobese diabetic (NOD) mouse involves at least 17 Idd loci. Idd1 has been mapped to a class II gene in the major histocompatibility complex (MHC), whereas the products and functions of the remaining Idd loci are unresolved. To investigate how non-MHC Idd genes regulate islet inflammation and IDDM progression, NOD mice were compared with the nonobese diabetes-resistant (NOR) mouse, a related MHC-identical strain that possesses a subset of the NOD-derived alleles at the Idd loci. Using quantitative reverse transcriptase-polymerase chain reaction amplification and immunohistochemistry, we observed that disease resistance in NOR mice is reflected by a protracted block at the earliest stage of insulitis. In NOD islets, early antigen-presenting cell (APC) recruitment to islet lesions was temporally coincident with progressive T-cell infiltration. In striking contrast, islet infiltrates in NOR mice were composed of APCs with minimal contribution from T-cells and T-cell-derived inflammatory cytokines, conferring apparent resistance to invasive insulitis and beta-cell destruction. This is the first evidence that a subset of Idd susceptibility loci independently regulate T-cell and APC participation in insulitis progression. As progress is made toward identification of the Idd gene products, it will be crucial to determine how they regulate diabetogenesis. Our data define distinct cellular stages of IDDM pathogenesis in which the impact of Idd genes can be readily analyzed.
Diabetes 1998 Mar
PMID:Independent genetic regulation of T-cell and antigen-presenting cell participation in autoimmune islet inflammation. 951 36

Vascular endothelial growth factor (VEGF)/vascular permeability factor is a likely angiogenic mediator in proliferative diabetic retinopathy, and its role is under scrutiny in the pathogenesis of the capillary leakage characteristic of background diabetic retinopathy. To examine whether the diabetic milieu induces or increases retinal VEGF expression in humans, we examined retinas from nondiabetic eye donors and donors with 9 +/- 5 years of diabetes and documented microangiopathy. To identify possible confounding effects of the postmortem period, we also studied the postmortem stability of the VEGF transcript and the expression of the VEGF protein in rat retinas. In both human and rat retina we detected by Northern analysis a 4.2-kb VEGF mRNA species and by reverse transcriptase polymerase chain reaction the transcripts encoding VEGF165 (the most abundant), VEGF121, and VEGF189. By in situ hybridization and immunohistochemistry VEGF mRNA and protein co-localized at the ganglion cell, inner nuclear, and outer plexiform layers and in the walls of the blood vessels (where mRNA was scarce). The protein was additionally detected in photoreceptors. The abundance and distribution of VEGF mRNA and protein were not altered in the diabetic retinas, indicating that the diabetic environment is not sufficient to increase retinal VEGF expression. The demonstration that VEGF is constitutively expressed in the adult retina and is localized to discrete neural cells and their processes proposes a role for the cytokine in retinal homeostasis and/or function.
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PMID:Expression of vascular endothelial growth factor in the human retina and in nonproliferative diabetic retinopathy. 962 50

One requirement prior to xenotransplantation of porcine islets during Type 1 diabetes is to eliminate the risk of transmitting infectious agents, particularly retroviruses, even when specific pathogen-free (SPF) pigs are used. We developed two sensitive complementary PCR-derived detection tests to assess this risk. This first is intended to detect a novel endogenous retrovirus pol sequence related to a recently described human endogenous retrovirus (HERV-L) and to foamy retroviruses. Primers for species-specific detection of this porcine endogenous sequence were designed and tested. The second test is a product-enhanced reverse transcriptase (PERT) assay optimised for the detection of porcine reverse transcriptase activity. These tests, which were used to detect HERV-L-related sequences and reverse transcriptase activity in certain SPF pig cells and porcine cell lines, may be useful in studying the risk of transmitting retroviruses by pig islet xenotransplantation in the immunogenetic context of Type 1 diabetes.
Diabetes Metab 1998 Nov
PMID:Detection of porcine endogenous retrovirus: possible involvement in pig islet xenotransplantation. 988 Dec 42

Because programmed cell death (PCD) is an important mode of pericyte dropout in human diabetic retinopathy, whether increased oxidative stress in cells with diminished antioxidant defenses plays a causative role in the PCD process in diabetic pericytes has been studied. Ten diabetic and eight non-diabetic eye-bank eyes from 5 diabetic and 4 non-diabetic patients were included in this study. From individual neural retinas pericytes were isolated by a newly developed immunomagnetic technique. Total mRNA of the purified pericytes was isolated for quantitative reverse transcriptase (RT)-PCR assay. mRNA levels of a death protease (CPP32), the major enzyme that initiates the proteolytic cascade leading to cell death, were determined in association with the expression of antioxidative enzymes including glutathione peroxidase (GSH-Px), glutathione reductase, CuZn superoxide dismutase (SOD), MnSOD and catalase genes in pericytes. In comparison with pericytes from non-diabetic retinas, pericytes from diabetic retinas highly expressed CPP32 genes (4 +/- 0.6 fold increase, p < 0.01, n = 9). In diabetic pericytes, up-regulation of glutathione peroxidase (GSH-Px) (8.2 +/- 0.9 fold increase, p < 0.01, n = 9) and down-regulation of glutathione reductase (Gr) (4.1 +/- 0.4 fold decrease, p < 0.05, n = 9) and CuZnSOD (2.1 +/- 0.7 fold decrease, p < 0.05, n = 9) were observed. mRNA levels of MnSOD and catalase of diabetic pericytes did not differ significantly from those of non-diabetic pericytes. Overexpression of a member of interleukin-1 beta-converting enzyme (ICE) family, CPP32, indicated that the pericytes from diabetic retinas are in a "pre-PCD" state. This is the first evidence that the ICE family of death proteases is involved in pericyte dropout in diabetes. In these pre-PCD cells, the expression of antioxidant enzyme genes also was changed. Up-regulation of GSH-Px indicates a compensation mechanism to meet the demand of excessive glutathione in reduced form. Decreased levels of both glutathione reductase and CuZnSOD, despite the oxidative stress in the diabetic condition, suggest the breakdown of the antioxidant defense in pericytes. Most importantly, the altered gene profile of scavenging enzymes under diabetic conditions, correlating with overexpression of the cell death protease gene, together suggest increased oxidative stress as an etiological agent of pericyte dropout in diabetic retinopathy.
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PMID:Altered mRNA levels of antioxidant enzymes in pre-apoptotic pericytes from human diabetic retinas. 1009 40

Reovirus type 2 (Reo-2) infection in DBA/1 suckling mice causes insulitis, which leads to pancreatic islet-cell destruction, resulting in a diabetes-like syndrome. T-helper (Th) 1 cytokines are thought to play a key role in islet inflammation in insulin-dependent diabetes mellitus. We examined this hypothesis in the Reo-2-induced diabetes-like syndrome. We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. The treatment of monoclonal antibody (mAb) against mouse IFN-gamma during the expansion phase of insulitis (5-9 days after infection) inhibited the development of insulitis and the elevation of blood glucose concentrations in a dose dependent manner. Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. These results suggest that Reo-2-triggered autoimmune insulitis may be mediated by Th1 lymphocytes and IFN-gamma may play a role in islet inflammation leading to islet cell destruction.
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PMID:Interferon-gamma plays a role in pancreatic islet-cell destruction of reovirus type 2-induced diabetes-like syndrome in DBA/1 suckling mice. 1019 14

To determine whether glucagon-like peptide (GLP)-1 increases insulin sensitivity in addition to stimulating insulin secretion, we studied totally depancreatized dogs to eliminate GLP-1's incretin effect. Somatostatin was infused (0.8 microg x kg(-1) x min(-1)) to inhibit extrapancreatic glucagon in dogs, and basal glucagon was restored by intraportal infusion (0.65 ng x kg(-1) x min(-1)). To simulate the residual intraportal insulin secretion in type 2 diabetes, basal intraportal insulin infusion was given to obtain plasma glucose concentrations of approximately 10 mmol/l. Glucose was clamped at this level for the remainder of the experiment, which included peripheral insulin infusion (high dose, 5.4 pmol x kg(-1) x min(-1), or low dose, 0.75 pmol x kg(-1) x min(-1)) with or without GLP-1(7-36) amide (1.5 pmol x kg(-1) x min(-1)). Glucose production and utilization were measured with 3-[3H]glucose, using radiolabeled glucose infusates. In 12 paired experiments with six dogs at the high insulin dose, GLP-1 infusion resulted in higher glucose requirements than saline (60.9+/-11.0 vs. 43.6+/-8.3 micromol x kg(-1) x min(-1), P< 0.001), because of greater glucose utilization (72.6+/-11.0 vs. 56.8+/-9.7 micromol x kg(-1) x min(-1), P<0.001), whereas the suppression of glucose production was not affected by GLP-1. Free fatty acids (FFAs) were significantly lower with GLP-1 than saline (375.3+/-103.0 vs. 524.4+/-101.1 micromol/l, P<0.01), as was glycerol (77.9+/-17.5 vs. 125.6+/-51.8 micromol/l, P<0.05). GLP-1 receptor gene expression was found using reverse transcriptase-polymerase chain reaction of poly(A)-selected RNA in muscle and adipose tissue, but not in liver. Low levels of GLP-1 receptor gene expression were also found in adipose tissue using Northern blotting. In 10 paired experiments with five dogs at the low insulin dose, GLP-1 infusion did not affect glucose utilization or FFA and glycerol suppression when compared with saline, suggesting that GLP-1's effect on insulin action was dependent on the insulin dose. In conclusion, in depancreatized dogs, GLP-1 potentiates insulin-stimulated glucose utilization, an effect that might be contributed in part by GLP-1 potentiation of insulin's antilipolytic action.
Diabetes 1999 May
PMID:Glucagon-like peptide 1 increases insulin sensitivity in depancreatized dogs. 1033 9

Uncoupling protein 2 (UCP-2) mRNA expression has been shown to be altered by metabolic conditions such as obesity in humans, but its functional significance is unknown. The expression of UCP-2 mRNA and protein in normal rat islets was established by reverse transcriptase-polymerase chain reaction and immunocytochemistry in pancreatic islets and tissue, respectively. Intense immunostaining of UCP-2 correlated with insulin-positive ,-cells. Overexpression of UCP-2 in normal rat islets was accomplished by infection with an adenovirus (AdEGI-UCP-2) containing the full-length human UCP-2 coding sequence. Induction of the AdEGI-UCP-2 gene resulted in severe blunting of glucose-stimulated insulin secretion (GSIS) without affecting islet insulin content or the ability of the calcium ionophore A23187 to increase insulin secretion from AdEGI-UCP-2-expressing islets. Therefore, UCP-2 overexpression affects signal transduction proximal to Ca2+-mediated steps, including exocytosis. Insulin secretion from single beta-cells to 16.5 mmol/l glucose examined by reverse hemolytic plaque assay was nearly ablated if UCP-2 was overexpressed. Thus, a direct, causal relationship between overexpression of UCP-2 and inhibition of GSIS in normal islets has been established. These data suggest that increased expression of UCP-2 has the potential to cause the lack of a glucose effect on insulin secretion in type 2 diabetes.
Diabetes 1999 Jul
PMID:Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets. 1038 58

With the development of more potent and better tolerated antiretroviral regimens, durable antiviral responses are being observed in an increasing fraction of patients. Substantial benefits are associated with these responses: Initially memory, then naive, CD4 cell counts may rise by 150-200 cells/mm3; CD8 cell numbers also rise sharply but then fall below pretreatment levels, presumably as antigenic stimuli driving the CD8 response decline; cellular activation markers decline; distortions in the T cell repertoire gradually lessen; and increases in proliferative responses to mitogens and recall antigens are more easily elicited. Clinical benefits directly accompany these immunologic benefits. Other than peripheral neuropathy, few long-term toxicities are associated with nucleoside analogue reverse transcriptase inhibitors. Recent reports, however, link protease inhibitors with hyperlipidemia, redistribution of body fat, and diabetes mellitus. As more human immunodeficiency virus type 1-infected persons receive long-term antiviral maintenance therapy, successful management of these toxicities will require more attention.
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PMID:Longer-term immunologic effects and side effects of successful antiretroviral therapy. 1043 60

During 1997 a large dengue epidemic occurred in Rio Grande do Norte, a State in north-east Brazil. The co-circulation of dengue virus type 1 and dengue virus type 2 was demonstrated by virus isolation in Aedes albopictus clone C6/36 cell-line and by reverse transcriptase-polymerase chain reaction (RT-PCR). IgM capture enzyme-linked immunosorbent assay confirmed 52.3% of the 8105 studied cases and dengue antigen was demonstrated by immunohistochemical reaction on hepatocytes from 2 out of 5 fatal cases studied. Individual risk factors for development of dengue haemorrhagic fever/dengue shock syndrome, such as hypertension, diabetes mellitus and bronchial asthma, are discussed.
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PMID:Dengue epidemic in the State of Rio Grande do Norte, Brazil, in 1997. 1049 50


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