Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synthetic oligonucleotide probes were designed to detect the alpha-subunits of the guanine-nucleotide-regulatory proteins (G-proteins) Gi-1, Gi-2, Gi-3 and Gs (Gi is inhibitory and Gs is stimulatory). Each probe detected a single major mRNA species in Northern blots of RNA extracted from a variety of tissues. A probe was designed to identify the two forms of G-protein beta-subunits, beta 1 and beta 2. This probe hybridised with a single 1.8-kb transcript (beta 2) in RNA from all tissues studied except for brain, where a less-abundant 3.4-kb transcript (beta 1) was also detected. These probes were used to assess whether the induction of diabetes, using streptozotocin, altered the levels of mRNA coding for specific G-protein components. In hepatocytes, diabetes caused a significant reduction in the number of transcripts coding for alpha-Gs, alpha-Gi-2 and alpha-Gi-3; mRNA for alpha-Gi-1 was undectable. In adipocytes, diabetes increased dramatically the mRNA coding for alpha-Gi-1 and alpha-Gi-3, whilst no significant changes occurred in the fractions coding for alpha-Gi-2 and alpha-Gs. No significant changes in the mRNA coding for G-protein alpha-subunits were observed in either brain, heart, skeletal muscle or kidney. Diabetes did not cause any significant changes in the mRNA coding for beta 2 in any tissue or cell population studied. Such results on the relative levels of mRNA encoding G-protein components was obtained by comparing equal amounts of total RNA from tissues of control and diabetic animals. G-protein mRNA levels were expressed relative to ribosomal 28S RNA levels and, in some instances, relative to transcripts for a structural protein called CHO-B. The total cellular levels of both RNA and DNA were assessed in the various tissues and cells studied. Major falls in RNA levels/cell appeared to occur in hepatocytes and to a lesser extent in adipocytes and skeletal muscle. Thus major reductions in G-protein transcripts occurred in hepatocytes. The detected changes in G-protein mRNA are discussed in relation to the available evidence on G-protein expression. We suggest that diabetes causes tissue-specific changes in the levels of mRNA for particular G-protein species; this may have consequences for the functioning of cellular signal-transduction mechanisms in the affected tissues.
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PMID:Diabetes-induced changes in guanine-nucleotide-regulatory-protein mRNA detected using synthetic oligonucleotide probes. 169 58

beta-Blockers are effective in reducing the blood pressure of many patients with systemic hypertension. They differ in terms of the presence or absence of intrinsic sympathomimetic activity, membrane-stabilising activity, beta 1-selectivity, alpha-blocking properties, and relative potency and duration of action. All beta-blockers appear to have blood pressure lowering effects. The choice of which beta-blocker to use in an individual patient is determined by the pharmacodynamic and pharmacokinetic differences between the drugs in conjunction with the patient's other medical condition(s). This review discusses the practical use of beta-blockers and provides rational suggestions for which drug(s) to use in selected patient groups (Black, elderly, postinfarction, diabetes, renal disease, obstructive lung disease, elevated lipid levels, coexisting angina, and left ventricular hypertrophy).
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PMID:Clinical use of beta-adrenoceptor blockade in systemic hypertension. 197 82

The anatomic distribution of fat is related to the risk for obesity-associated morbidity. Among individuals with equal degrees of relative adiposity, those with an upper-body preponderance of fat distribution (android) have higher rates of diabetes, stroke, ischemic heart disease, and early death than those with preferential deposition of adipose tissue in lower portions of the body (hips, thighs, buttocks; gynecoid. There are well-documented anatomic site-related differences in the relative activities of the adrenergic receptors (beta 1----lipolysis; alpha 2----antilipolysis) that control lipolysis. We assessed modifications of the status of alpha 2- and beta 1-adrenergic receptor and subreceptor function in small fragments of adipose tissue obtained by needle biopsy from the gluteal and abdominal subcutaneous regions of five android, seven gynecoid, and six uniformly obese women during a period of weight maintenance (4 weeks) (T1), and after 15% weight loss on an 840 kcal/d diet (T2). Measurements of body shape and adipocyte size were made and related to changes in the metabolism of these adipocytes. The waist-to-hip ratio (WHR) was used to define these three types of regional distribution of fat in these obese subjects: android = WHR greater than 0.86; gynecoid = WHR less than or equal to 0.76; uniform = WHR greater than 0.76 less than or equal to 0.86. WHR was not significantly altered by weight loss in any of the three groups. Although significant effects of time and/or anatomic site on in vitro responses to isoproterenol, norepinephrine, clonidine, forskolin, and dibutyryl cAMP were found, these did not correlate with intra-individual changes in anthropometry or adipocyte size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional changes in adrenergic receptor status during hypocaloric intake do not predict changes in adipocyte size or body shape. 215 70

To investigate the autoimmune pathogenesis of spontaneously occurring diabetes mellitus in BB rats, spleen cells of newly diagnosed diabetic BB rats were fused with mouse myeloma cells. Hybridoma supernatants were screened for antibodies by indirect immunofluorescence and by 51Cr-release assays using the RINm5F rat insulinoma cell line. One clone, E5C2, produced an IgM kappa antibody that was cytotoxic for RINm5F cells, but not for other rat cell lines nor for primary rat islet cells. However, treatment of primary rat islet cells with neuraminidase exposed surface antigens and rendered the cells susceptible to complement-mediated lysis by antibody E5C2. Using immunostaining of glycolipids separated by thin-layer chromatography, hapten inhibition assays with defined carbohydrates, and Western blots, the antigens recognized by E5C2 on RINm5F cells were identified as glycoproteins with molecular weights of 60,000 and 68,000. The antibody recognizes a carbohydrate antigen containing the sequence Gal beta 1-4GlcNAc-R, which on RINm5F cells is predominantly hidden by covalently bound sialic acid. These studies raise the possibility that hidden antigenic determinants on islet cells exposed by a variety of means may be the target of autoimmune attack.
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PMID:Pancreatic islet cell surface glycoproteins containing Gal beta 1-4GlcNAc-R identified by a cytotoxic monoclonal autoantibody. 243 47

The adrenergic control of carbohydrate metabolism is expressed at two levels: regulation of substrate flow, and interference with the secretion of hormones. Normally, this adrenergic regulatory system only plays a minor role. However, it is of great importance as an acute adaptation of the body to fight and flight. Under these circumstances, fuel fluxes increase almost instantaneously. Glycogenolysis and gluconeogenesis are responsible for increased hepatic glucose output. Increased fatty acid flux is brought about by stimulated adipose tissue lipolysis, which probably, as a secondary phenomenon, causes decreased peripheral glucose utilisation by the skeletal muscle mass. Cerebral glucose uptake accounts for half the body's basal glucose production. Since this glucose uptake is concentration-dependent only, hypoglycaemia rapidly leads to cerebral dysfunction. To guarantee cerebral glucose uptake, the body has a dual defense mechanism against hypoglycaemia: hormonal and metabolic counteraction. The first consists of the secretion of glucagon and (nor)epinephrine, the latter of hepatic autoregulation and alternative fuels for noncerebral tissues. In clinical practice, the inappropriate insulin-excess state forms the major cause of hypoglycaemia. There is, however, a second reason why patients with diabetes mellitus are at risk. Diabetes by itself leads to impaired glucagon secretion and, when autonomic neuropathy exists, to diminished (nor)epinephrine secretion. Thus, interference with the latter, such as administration of beta-blocking agents, further impairs hypoglycaemic counterregulation. In fact, numerous studies document delayed recovery from experimentally induced hypoglycaemia in diabetic patients receiving beta-blocking agents. However, using beta 1-selective blocking agents, mean recovery from hypoglycaemia in groups of diabetic patients demonstrates minor delay only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-blockade and carbohydrate metabolism: theoretical aspects and clinical implications. 243 7

Since beta-adrenoceptor blocking drugs were originally discovered and shown to be important therapeutic agents in the management of both angina pectoris and hypertension, many other similar drugs have become available. These share the common property of beta-adrenoceptor antagonism, though they may vary in terms of potency. However, they differ from one another in terms of their additional pharmacological properties--cardioselectivity, partial agonist activity, and membrane stabilizing activity. Cardioselectivity refers to the ability of some drugs, notably atenolol and metoprolol, to block beta 1 receptors without blocking beta 2 receptors. This has been considered to be of potential importance in patients with obstructive airways disease, patients with peripheral vascular disease, and patients with insulin-dependent diabetes during hypoglycemic crisis. Partial agonist activity is the intrinsic activity that some drugs have to stimulate the beta adrenoceptor while they are competitively antagonizing catecholamines. In consequence, they may have less effect on resting heart rate, cardiac output, peripheral vascular blood flow, and resting respiratory function. However, there is no good evidence that major adverse effects of beta-adrenoceptor blocking drugs such as congestive heart failure, bronchospasm, or symptoms of peripheral vascular disease are prevented by drugs with partial agonist activity: bradycardia may be improved, but its importance has probably been overemphasized. Membrane-stabilizing activity appears to be unimportant. As far as pharmacokinetic differences between drugs are concerned, lipid solubility is seen to be of increasing importance. The more water-soluble drugs have longer elimination half-lives, produce less interindividual variation in steady-state plasma concentrations, and penetrate the central nervous system less readily.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological characteristics of beta blockers and their role in clinical practice. 243 20

The primary goals in the management of hypertension, angina pectoris, and postinfarction cases are to prevent further damage to the cardiovascular system and to reduce the risk of subsequent myocardial infarction. Of all the drugs currently available, the beta-blockers seem the most likely to achieve this aim. The search for new beta-blockers centers around the need for agents that offer the advantages of beta 1-adrenoceptor antagonism without the unwanted beta 2 effects, which may be dangerous in asthmatic patients and may make bronchitis, diabetes, and arteriopathy worse or more difficult to control. One solution is to use a selective beta 1-adrenoceptor antagonist. Another is to develop a molecule that acts as an antagonist at beta 1-adrenoceptors and as an agonist at beta 2-adrenoceptors. celiprolol is such a "third-generation" beta-blocker in that it combines both attributes, and thereby offers a clinically relevant advance. It does not seem to disrupt glucose homeostasis or exacerbate peripheral vascular disease, the lipid profile appears to be positively altered, and the risk of bronchospasm is reduced. Celiprolol is therefore both clinically and biochemically well tolerated.
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PMID:Pharmacology of third-generation beta-blockers: greater benefits, fewer risks. 248 89

We examined the clinical usefulness determined by polyacrylamide gel electrophoresis, followed by reaction with peroxidase-coupled lectins using urinary glycoproteins for diabetic nephropathy in 20 patients with diabetes mellitus. Lectins used were Triticum vulgaris (WGA), Phaseolus vulgaris (PHA-E4), Dolichos biflorus (DBA), and Lens culinaris (LCA), which have high affinity for beta 1----4N-acetyl-D-glucosamine (GlcNAc beta 1----4GlcNAc), N-acetyl-D-galactosamine (GalNAc), alpha-galactosamine (alpha-GalNAc), and alpha-mannose (alpha-Man) residues, respectively. Electrophoretic patterns of urinary glycoproteins clearly showed the presence of lectin-reactive glycoproteins with molecular weights lower than that of albumin. The molecular weight of the main bands reacted with WGA, PHA-E4 or LCA were 50,000 and 38,000, and increased with the progress of diabetic nephropathy. WGA reacted strongly with many glycoproteins having a wide range of molecular weights. LCA and PHA-E4 reacted preferentially with glycoproteins of molecular weights glycoproteins of molecular weights lower than 50,000, but no reaction was observed by DBA. These results suggest that low molecular urinary glycoproteins have abundant carbohydrate residues such as GlcNAc beta 1----4GlcNAc, GalNAc, and alpha-Man. The excretion of low molecular weight glycoproteins with high affinities for some lectins suggests functional impairment in diabetic nephropathy.
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PMID:[Electrophoretic analysis of urinary glycoproteins in diabetic nephropathy using peroxidase-lectins]. 248 79

In streptozotocin induced diabetes in rats, excretion of urinary protein fractions were studied in relation to structural changes in the renal glomeruli, using light and transmission electron microscopy. After six weeks of induced diabetes only beta 1 and beta 2 plasma globulins were significantly elevated. The amount of excreted proteins and degree of glomerular changes were not proportional. In the initial stages (1-2 weeks) glomerular structural changes were very mild and were accompanied by significantly elevated proteinuria. This progressed (4-8 weeks) to moderate to prominent structural changes with intermittent proteinuria except for the fractions beta 1 & beta 2 which were elevated throughout the duration of the experiment. The amount of proteinuria was not proportional to changes in the plasma protein levels. The following conclusions may be made: 1) The mild early glomerular abnormalities seem to be mainly due to acute metabolic disturbances. 2) An early indication of diabetic nephropathy is provided not only by albuminuria, but may also be an elevated excretion of beta-globulin fractions. 3) Decrease of albuminuria in the later stages of diabetes may be related to the deposition of albumin as a basement membrane-like material in the mesangium.
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PMID:Structural changes in glomeruli and proteinuria in streptozotocin diabetic rats. 252 Apr 52

Type 1 diabetes results from the destruction of insulin-producing pancreatic beta cells. Genetic and environmental factors are implicated in the beta cell destruction. As environmental factors affecting the induction of type 1 diabetes, diabetogenic viruses, chemicals, toxins, and diet are likely candidates as either primary injurious agents of beta cells or triggering agents for the induction of autoimmunity. Regarding viruses as a triggering factor of type 1 diabetes, there are at least two different pathogenic mechanisms in virus-induced diabetes: cytolytic infection of beta cells, leading to their destruction, and triggering of autoimmunity, leading to the autoimmune-mediated destruction of beta cells. Since there is no correlation between the induction of antibodies to Coxsackie B viruses and the presence of islet cell autoantibodies in patients with type 1 diabetes, the induction of diabetes by Coxsackie B viruses may be due to cytolytic infection of beta cells rather than an autoimmune response. In contrast, rubella virus and cytomegalovirus (CMV) do appear to be somehow associated with autoimmune type 1 diabetes since there is a strong correlation between the presence of islet cell autoantibodies and persistent infections. Regarding genetic factors, there are distinct markers related to the susceptibility to Coxsackie B4 virus-associated type 1 diabetes and CMV-associated type 1 diabetes. Four specific DNA restriction endonuclease fragments (BamHI-DQ-beta 6.6, TaqI-DR-beta 4.3, TaqI-DR-beta 2.5 and TaqI-DR-beta 1.5 kb) are related to the susceptibility to Coxsackie B4 virus-associated type 1 diabetes while six specific DNA restriction endonuclease fragments (BamHI-DQ-alpha 12.5, -beta 3.7 and -beta 3.2 kb, TaqI-DQ-alpha 7.2, -beta 7.2 and -beta 5.4 kb) are related to the susceptibility to CMV-associated type 1 diabetes.
Diabetes Res Clin Pract 1989
PMID:Viruses as a triggering factor of type 1 diabetes and genetic markers related to the susceptibility to the virus-associated diabetes. 268 Mar 67


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