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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transport specificity of L-glutamine influx in the perfused rat exocrine pancreas has been investigated using a dual isotope tracer dilution technique. During a single circulation through the isolated pancreas, an epithelial uptake of 71 +/- 1% (n = 10) was measured for L-(3H)glutamine relative to the extracellular marker D-(14C)mannitol. L-(3H)glutamine uptake was markedly inhibited during perfusion with 10 mM L-glutamine, L-histidine, L-methionine, L-serine, or L-cysteine. The system A--specific analogue alpha-methylaminoisobutryic acid and L-glutamic acid were ineffective inhibitors. L-Glutamine transport was saturable (0.05 - 32 mM), with an apparent Kt = 14 +/- 1 mM and Vmax = 13.4 +/- 0.7 mumol/min g (n = 6), and largely insensitive to perfusion with 1 mM ouabain or a sodium-free solution. In kinetic inhibition experiments, the Vmax/Kt ratio for L-glutamine remained unaltered during perfusion with 10 mM L-serine, whereas L-glutamine appeared to inhibit L-serine transport noncompetitively. Tracer L-glutamine efflux was enhanced by increasing concentrations of unlabeled L-glutamine and 10 mM L-serine. Similarly, tracer L-serine efflux was accelerated in the presence of 10 mM L-glutamine. Unlike L-serine, the transport activity for L-glutamine was not stimulated by 100 microU/ml exogenous insulin or streptozotocin-induced experimental diabetes. These findings suggest that in the exocrine pancreas, L-glutamine transport is mediated primarily by a large neutral system L.
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PMID:Characteristics of L-glutamine transport in the perfused rat exocrine pancreas: lack of sensitivity to insulin and streptozotocin-induced experimental diabetes. 310 60

Phosphatidylethanolamine (PE) N-methylation was studied in skeletal muscle sarcoplasmic reticulum (SR) 6 wk after the induction of experimental diabetes in rats by an injection of streptozocin (65 mg/kg iv). A significant increase in the incorporation of radiolabeled methyl groups from S-adenosyl-L-methionine (AdoMet) into intramembranal PE was observed in diabetic preparations at 0.055 microM AdoMet, whereas the methylation activity was unaltered at 10 and 150 microM AdoMet concentrations. The increase in PE N-methylation activity was not evident until 28 days after streptozocin injection and was normalized by a 2-wk treatment of diabetic animals with insulin. In the presence of 10 microM of ATP and low concentrations of Ca2+ (0.1 microM), PE N-methylation was maximally activated, but the percent increase was similar in control, diabetes, and insulin-treated diabetes; at 100 microM Ca2+, however, N-methylation activity was depressed only in diabetic preparations. Calmodulin inhibitors such as compound 48/80 and calmidazolium (compound R24571) abolished the effect of Ca2+ and ATP on PE N-methylation in all three groups. Sarcolemmal (SL) PE N-methylation in diabetic skeletal muscle was also found to be increased at 0.055 microM AdoMet. The results suggest that intramembranal calmodulin may participate in regulating PE N-methylation in skeletal muscle membranes, but it may not be responsible for the high N-methylation activity in diabetic rats.
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PMID:Increased SR phospholipid N-methylation in skeletal muscle of diabetic rats. 313 15

Levels of methionine-enkephalin immunoreactivity (MEI) and beta-endorphin immunoreactivity (BEI) were measured by means of a specific RIA in pituitary, hypothalamus, pancreas, and adrenal glands of db/db and control mice. We found significantly higher levels of MEI in the pituitaries of db/db mice than in either littermate or background strain controls. There was no significant difference in MEI levels in pancreas, adrenal glands, and hypothalamus. There was a significant difference in the BEI levels in the pituitaries of db/db mice compared with those in controls. No significant difference in BEI levels was observed between db/db and control mice in any of the other regions examined. We conclude from the above data that the opiate peptide system in the hypophyseal-hypothalamic axis of the db/db mouse is abnormal and warrants further investigation. The significance of this finding with respect to the possible etiology of diabetes mellitus is discussed.
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PMID:Methionine-enkephalin and beta-endorphin levels in brain, pancreas, and adrenals of db/db mice. 315 53

We have previously used rat hepatic messenger ribonucleic acid (mRNA) activity profiles to categorize various pathophysiologic states. To test the hypothesis that similar techniques can be used to categorize disease states in humans, we examined the mRNA activity profiles by using in vitro translational assays of Ficoll-Hypaque-separated mononuclear cells obtained from six normal volunteers, six patients with type I diabetes, and five patients with type II diabetes as example of different disease states. Translated proteins were labeled with sulfur 35-labeled methionine, separated by two-dimensional gel electrophoresis, and quantitated by videodensitometry of autoradiographs derived from the two-dimensional gels. Of approximately 160 quantitated mRNAs, the levels of 12 were found to be altered in one of the diabetic states. The values of nine were changed in patients with type I diabetes and the values of 11 were altered in patients with type II diabetes. Although the values of most mRNAs increased, significant decreases were also observed. Moreover, four spots showed significant differences in response between the two diabetic states. Discriminant analysis allowed the separation of all three states. Finally, several mRNAs also displayed an age-related correlation. We have demonstrated that unstimulated mononuclear cell mRNAs can be used to study the effects of pathophysiologic states on gene expression in humans. Furthermore, our results support the potential use of this issue to study the effect of a wide variety of disease states on gene expression.
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PMID:Human lymphocyte messenger RNA activity profiles in type I and type II diabetes: a tool for classification of metabolic disease. 318 94

An initial transient hyperglycemia was seen in mice injected with asparagine, fluoroacetate, hydroxylamine, or malonate plus methionine, whereas an initial triphasic blood glucose response and a transient "secondary" hyperglycemia were exhibited in those injected with hydroxylamine plus arsenite, and a delayed hypoglycemia was observed in those treated with fluoroacetate or arsenite. The glucose-induced insulin secretion was significantly decreased in isolated pancreatic islets incubated with hydroxylamine plus arsenite. Light and electron microscopy, pyroantimonate technique, and X-ray microanalysis disclosed mitochondrial damage, degeneration, and necrosis among the beta-cells in the islets of mice injected with hydroxylamine plus arsenite. Glycogen depletion and microvesicular fatty change were seen in the liver of mice treated with fluoroacetate, arsenite, or hydroxylamine plus arsenite. These observations support the view that inhibition of the activity of citric acid cycle enzymes and associated reactions in the beta-cells play a role in the induction of diabetic features.
Diabetes 1988 Jan
PMID:Structural beta-cell changes and transient hyperglycemia in mice treated with compounds inducing inhibited citric acid cycle enzyme activity. 327 58

The effects of hypoinsulinemic nonketotic streptozotocin diabetes on hepatic apo B synthesis and secretion was studied in primary cultures of rat hepatocytes. Diabetic rats were characterized by their significantly elevated serum glucose, apo B, and triglyceride levels, while serum insulin levels were less than a third of normal. Serum transminase activities of diabetic rats were significantly elevated when compared with control rats, which was attributed to an increase in liver transaminase activity in diabetic rats. The pattern of enzyme activities of hepatocytes reflected that observed in livers of donor rats and the pattern was retained by primary cultures of hepatocytes over the culture period. Hepatocytes from diabetic rats secreted only one third of the apo B secreted by hepatocytes from control rats, which was determined by monoclonal immunoassay of rat total apo B. Decreases in secretion were confirmed by measurement of secretory [35S]methionine-labeled lipoprotein apo B radioactivity. The decreased apo B content of media of hepatocytes from diabetic rats was not due to increased apo B catabolism since hepatocytes from diabetic rats were shown to degrade less lipoprotein-apo B than hepatocytes from normal rats in control experiments. In addition, the apo B content of detergent-solubilized hepatocytes from diabetic rats was significantly less than that of hepatocytes from control rats. These results suggest that insulin is necessary for normal hepatic apo B synthesis and secretion and that the hyperlipidemia associated with hypoinsulinemia in vivo is primarily of intestinal origin.
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PMID:Effects of nonketotic streptozotocin diabetes on apolipoprotein B synthesis and secretion by primary cultures of rat hepatocytes. 329 89

Isolated pancreatic acini from streptozocin-induced diabetic rats were used to study the role of insulin on the synthesis of specific cellular proteins. When acini were incubated with 0-100 nM insulin for 2 h and then pulsed with [35S]methionine, a dose-dependent increase in [35S]methionine incorporation into total cellular proteins was observed. When acinar cell lysates were subjected to gel electrophoresis, 12 major newly synthesized protein bands were resolved. Insulin (100 nM) increased the incorporation of [35S]methionine into all bands but with significantly different rates, varying from 84 to 216% of control. Next, specific antibodies to amylase, trypsin, ribonuclease, myosin, and lactate dehydrogenase (LDH) were used to evaluate the biosynthesis of known proteins. Insulin stimulated labeled amino acid incorporation into amylase by 148% over control. Insulin stimulated the synthesis of trypsinogen to a similar degree, but ribonuclease synthesis showed a significantly smaller increase of 53% over control. Insulin stimulated myosin and LDH synthesis by 169 and 184%, respectively. A differential pattern of protein synthesis was also observed when acini were treated with two other stimulators of protein synthesis, cholecystokinin and hemin. Both of these stimulators had a reduced effect on ribonuclease synthesis compared with amylase and trypsinogen synthesis but failed to increase myosin synthesis. When the RNAs extracted from control acini and acini treated with 100 nM insulin were translated in vitro, the proteins synthesized were quantitatively similar. This study therefore indicates that insulin has translational effects on acinar protein synthesis, and these effects are nonparallel for various specific acinar cell proteins.
Diabetes 1987 Sep
PMID:Insulin and other stimulants have nonparallel translational effects on protein synthesis. 330 74

Total cytochrome P-450 levels rise in diabetic rats. Two specific forms of cytochrome P-450 that are elevated have been isolated from liver microsomes of streptozotocin-induced idabetic male rats. One enzyme, termed RLM6, metabolizes aniline and acetol, but not testosterone, in a reconstituted system with NADPH-cytochrome P-450 reductase. RLM6 is isolated as a high spin cytochrome with a minimum molecular weight of 53,500. It has a unique amino-terminal amino acid sequence lacking methionine at the amino-terminal position. Polyclonal antibodies to RLM6 recognized most other forms of cytochrome P-450 in Western blots, but could be made monospecific by adsorption to cross-reacting proteins coupled to Sepharose 4B. Using the monospecific antibodies, RLM6 was estimated to be present in microsomes of untreated male rats at 0.04 nmol/mg protein (5% of total P-450). In chronically diabetic rats this level rose to 0.35 nmol/mg protein and 24% of the P-450 content. Immunoreactive protein of molecular weight identical to RLM6 was elevated in microsomes of non-diabetic rats treated with ethanol, acetone, or isoniazid as well as in rats starved for 48 h. Insulin treatment of diabetic rats for 1 week lowered the immunologically detectable levels of RLM6 to levels found in the untreated rat. The other form of cytochrome P-450, RLM5b, does not metabolize aniline and only poorly metabolizes acetol and testosterone. This 52.5-kDa protein is isolated as a predominantly (60%) high spin enzyme. It has a unique NH2-terminal amino acid sequence with methionine as the terminal residue, and is present in untreated male rat liver microsomes at 0.16 nmol/mg protein. It is elevated in diabetes, like RLM6, but treatment with insulin for 1 week does not completely restore the microsomal content to that of the non-diabetic rat.
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PMID:Responses to insulin by two forms of rat hepatic microsomal cytochrome P-450 that undergo major (RLM6) and minor (RLM5b) elevations in diabetes. 330 89

The sera of type I (insulin-dependent) diabetic subjects are reported to contain autoantibodies against a 64,000-Mr protein identified in [35S]methionine biosynthetically labeled pancreatic islet cells. We have attempted to localize this autoantigen to the surface of the beta-cell and to define its properties. Sera from 10 newly diagnosed type I diabetic subjects, including five of the index sera originally used to identify the autoantigen, were shown to specifically precipitate a reduced protein of 67,000 Mr from Triton-solubilized, surface 125I-labeled cultured adult human islet and rat insulinoma (RINm5F) cells but not from fresh rat spleen cells. Further characterization revealed that this protein was bovine serum albumin (BSA) adsorbed to cells from fetal calf serum (FCS)-supplemented culture medium and precipitated by BSA antibodies present in many diabetic sera. No labeled proteins were specifically precipitated when surface 125I-labeled and solubilized human islet or RINm5F cells were precleared with anti-BSA immunoglobulins or when cells were first cultured in human serum. In contrast, a 64,000-Mr protein, clearly not BSA, was precipitated by diabetic globulins from human islets but not from RINm5F cells labeled with [35S]methionine. In addition, a protein of the same size as well as proteins of approximately 35,000, 43,000, 140,000, and 200,000 Mr were specifically precipitated by diabetic globulins from freshly isolated human islets solubilized in Triton X-100 and then labeled with 125I. These findings suggest that the 64,000-Mr antigen is not expressed on the surface of human islet cells, at least in culture, and therefore question its relevance as a target for islet cell surface antibodies in initiating beta-cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Dec
PMID:64,000-Mr autoantigen in type I diabetes. Evidence against its surface location on human islets. 331 89

There are conflicting reports concerning the existence of severe hypermethioninemia in rats made diabetic with the pancreotoxin, streptozotocin. To determine whether this discrepancy is due to experimental differences in the severity of diabetes or the diet fed to the animals, streptozotocin-diabetic and control rats were fed either a casein-based semipurified diet or laboratory chow for 2 or 5 weeks. Plasma methionine concentrations were elevated six- to nine-fold after 2 weeks in the casein-fed diabetics compared with both their own controls and the chow-fed diabetics, respectively. Circulating methionine levels had declined sharply by 5 weeks in the casein-fed diabetics but were still more than twice those of the casein-fed control and chow-fed diabetic levels. Since methionine intakes were only 30% greater in the casein-fed diabetics than in the chow-fed diabetics, it is unlikely that this is the sole cause of the large differences in plasma methionine levels. The reason for the difference in circulating Met levels could not be explained on the basis of overall amino acid availability, since growth, nitrogen balance, and plasma large neutral amino acid profiles (excluding Met) were similar within control and diabetic groups fed the two diets.
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PMID:The effects of diet and duration of diabetes on hypermethioninemia in streptozotocin-diabetic rats. 337 May 50


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