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)

Serine dehydratase was induced in the kidneys of normal rats by the administration of either glucagon or dexamethasone. The increase in enzyme activity was associated with an increase in both enzyme protein and its mRNA, which were determined respectively by Western blot and RNA blot analysis. No apparent differences were observed between kidney and liver in the molecular weights of serine dehydratase proteins and the sizes of their mRNAs. Although kidney serine dehydratase was dramatically induced by either glucagon or dexamethasone, the liver enzyme was induced by glucagon but not by dexamethasone alone in the intact rat. On the other hand, liver serine dehydratase was induced in starvation, diabetes mellitus, and a high-protein diet. The kidney enzyme could not be induced under any of these conditions.
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PMID:Regulation of the expression of the serine dehydratase gene in the kidney and liver of the rat. 238 71

The role of serine proteases of trypsin type was shown in the pathogenesis of autoimmune processes and nonspecific reactivity in diabetes mellitus. The use of protease blockers and thymic hormonal factors was proposed for patients suffering from diabetes mellitus with changed immunological reactivity.
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PMID:[Activity of serum and lymphocyte serine proteases of patients with diabetes mellitus and the possibility of using protease blockers in combined therapy]. 246 68

We have characterized a plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and a cytosolic phosphatidylinositol (PI)-specific PLC in human liver. Epinephrine, 1 x 10(-5) M, and vasopressin, 1 x 10(-8) M, stimulated PIP2-PLC which was enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). PI-PLC stimulation was not observed by these agents. Insulin and insulin-like growth factors (IGF-I and IGF-II) in the presence and absence of GTP gamma S did not stimulate PIP2-PLC or PI-PLC in plasma membranes and cytosol preparations nor phosphoinositide breakdown in isolated human hepatocytes. Furthermore, serendipitly we found that PIP2-PLC activity was increased in liver membranes from obese patients with type II diabetes when compared to obese and lean controls. We conclude that in human liver, insulin and IGFs are not members of the family of hormones generating inositol trisphosphate (IP3) as a second messenger. Furthermore, the increased PIP2-PLC in diabetic liver may result in: (a) increased intracellular concentrations of IP3 and thus increased Ca2+, which has been postulated to induce insulin resistance; and (b) increased diacylglycerol and thus increased protein kinase C which phosphorylates the insulin receptor at serine residues inactivating the insulin receptor kinase. While the mechanism of increased PIP2-PLC activity in diabetes is unknown, it may initiate a cascade of events that result in insulin resistance.
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PMID:Effect of insulin and insulin-like growth factors I and II on phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate breakdown in liver from humans with and without type II diabetes. 254 Jan 78

The effects of fasting, diabetes, cholestasis, two-third hepatectomy and adrenalectomy on the rat liver plasma membrane serine proteinase activity were studied. Our results show a significant decrease of the enzyme activity during fasting (-50%), during experimental diabetes (-50%), in regenerating liver after partial hepatectomy (-70%) and after extrahepatic cholestasis (-70%). No modifications are noted when the rats are bilaterally adrenalectomized. These findings suggest that the enzyme activity may be linked to the level of circulating insulin, and may be regulated in physiological cellular proliferation so as to prevent undesirable protein degradation.
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PMID:Pathophysiological variations in the rat liver plasma membrane serine proteinase activity. 261 51

RINmRH cells are a cloned cell line derived from a transplantable rat insulinoma. These cells display only some of the differentiated structure/function features of native pancreatic B-cells. In particular, they do not efficiently or reproducibly express islet B-cell surface antigens, which would otherwise render them useful for screening for the presence of anti-islet cell surface antibodies in the serum of suspected diabetic patients or their relatives. This study examines whether sodium butyrate can enhance expression of B-cell differentiation antigens on RIN cells. RIN cells were exposed to 1,2 or 4 mM butyrate for nine days, and cell growth followed. At 1 mM, butyrate inhibited cell growth by 90%. At the higher concentrations, there was a net loss in the number of cells per culture dish. Exposing the cells to 1 mM or 2 mM butyrate for two days, resulted in a 50% increase in cellular insulin content at the expense of a partial (1 mM) or complete (2 mM) loss of stimulated insulin release in response to glyceraldehyde or serine. A concentration of 1 mM butyrate was therefore used for subsequent studies. The binding to RIN cells of a panel of monoclonal antibodies (mAb's) known to bind native islet cells (R2D6, A2B5, A1D2, 3G5) as well as of serum from a diabetic patient known to carry anti-islet cell antibodies, was screened by cytofluorography or by a radio-binding assay. The relative binding affinity of the mAb's was 3G5 greater than A1D2 greater than A2B5 greater than R2D6. Only 2-3% of the cells were bound by the diabetic patient serum.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1989 Oct
PMID:Modulation by sodium butyrate of the differentiated status of a clonal pancreatic B-cell line (RIN). 269 45

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

In a preliminary experiment, we found a good correlation between 24-h urinary amino acid excretion and the 24-h average plasma levels of the same amino acids. Examining diabetics who were just beginning insulin therapy, we found that insulin normalized the abnormally high levels of excretion of branched-chain amino acids and serine. Interestingly, when expressed in terms of mol/g of creatinine, the normalization of serine excretion brought about by insulin was roughly equal to the normalization of glycine excretion brought about by insulin (-0.39 mM/g of creatinine vs. + 0.33 mM/g of creatinine over 24 h). Since plasma serine is primarily produced in the kidneys from glycine, this suggests that insulin affects the regulation of the serine-glycine metabolic pathway. In turn, measurement of urinary serine and glycine may provide a useful gauge of insulin activity in the tissues, including the kidneys.
Diabetes Res Clin Pract 1988 Sep 05
PMID:Rapid changes in urinary serine and branched-chain amino acid excretion among diabetic patients during insulin treatment. 314 95

A tissue kallikrein was purified from rat skeletal muscle. Characterization of the enzyme showed that it has alpha-N-tosyl-L-arginine methylesterase activity and releases kinin from purified bovine low-Mr kininogen substrate. The pH optimum (9.0) of its esterase activity and the profile of inhibition by serine-proteinase inhibitors are identical with those of purified RUK (rat urinary kallikrein). Skeletal-muscle kallikrein also behaved identically with urinary kallikrein in a radioimmunoassay using a polyclonal anti-RUK antiserum. On Western-blot analysis, rat muscle kallikrein was recognized by affinity-purified monoclonal anti-kallikrein antibody at a position similar to that of RUK (Mr 38,000). Immunoreactive-kallikrein levels were measured in skeletal muscles which have different fibre types. The soleus, a slow-contracting muscle with high mitochondrial oxidative-enzyme activity, had higher kallikrein content than did the extensor digitorum longus or gastrocnemius, both fast-contracting muscles with low oxidative-enzyme activity. Streptozotocin-induced diabetes reduced muscle weights, but did not alter the level of kallikrein (pg/mg of protein) in skeletal muscle, suggesting that insulin is not a regulator of kallikrein in this tissue. Although the role of kallikrein in skeletal muscle is unknown, its localization and activity in relation to muscle functions and disease can now be studied.
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PMID:Identification and characterization of a tissue kallikrein in rat skeletal muscles. 331 Oct 22

The effects of fasting, refeeding, and streptozotocin-induced experimental diabetes on free amino acid concentrations in the rat exocrine pancreas were investigated. Extracts of pancreatic tissue and plasma were analyzed using high-performance liquid chromatography (HPLC). Pancreatic and plasma concentrations of alanine were reduced in animals fasted for 24 to 72 h. Pancreatic concentrations of leucine, arginine, and glutamine were increased after fasting for 48 h, and concentrations of all essential amino acids plus the nonessential amino acids glycine, serine, taurine, and glutamine were elevated after fasting for 72 h. Refeeding 72 h fasted animals for 3 h or 24 h had a negligible effect on the plasma amino acid concentrations, but markedly lowered the concentration of essential amino acids within the pancreatic tissue. Diabetes lowered the total plasma amino acid concentration from 4.9 mM to 3.1 mM but increased the total pancreatic tissue amino acid level from 16.4 mM to 18.3 mM. Efflux of intracellular amino acids into the circulation of the isolated perfused pancreas was assessed under basal conditions and in response to a vascular amino acid challenge using HPLC. L-serine transstimulated efflux of a large number of amino acids, whereas cellular efflux was only minimally affected by L-phenylalanine. Fasting and diabetes-induced increases in essential amino acid concentrations within the pancreas may reflect decreased protein synthesis, accelerated protein catabolism, or a change in membrane transport. Altered intracellular amino acid levels may directly regulate exchange diffusion of intracellular for extracellular amino acid(s).
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PMID:Fasting, refeeding and diabetes modulate free amino acid concentrations in the rat exocrine pancreas: role of transstimulation in amino acid efflux. 336 44

We determined by the ninhydrin method the plasma amino acid (AA) levels prior to, during and following, a 1-hour i.v. infusion of 1 U/kg body weight each of secretin and pancreozymin in patients with normal (n = 74) or reduced (n = 39) exocrine pancreatic function, as assessed by the duodenal aspiration test. The results of the two tests correlated significantly with each other (p less than 0.001). A maximum AA decrease of greater than or equal to 12% was observed in all patients with a normally functioning pancreas (specificity 100%), and of less than 12% in all patients with medium to high-grade impairment of pancreatic function (sensitivity 100%). Since, however, low-grade pancreas insufficiency (20-40% of the mean normal enzyme output) is recognized in fewer than one-half of the cases, the overall sensitivity of the AA-consumption test decreases to 69%. The results can, however, be improved by: 1) Calculating the mean percentage AA decrease with a limit value of 5% (sensitivity 90%); 2) determining individual AA with pancreas-specific absorption, such as serine (sensitivity 92%); 3) dropping the lower normal value of exocrine pancreatic function to 25% of the normal mean enzyme output (sensitivity 96%). Diseases that may be associated with the most common condition that causes pancreatic insufficiency--chronic pancreatitis--and which have an influence on AA metabolism, such as cirrhosis of the liver and diabetes mellitus, have no influence on the accuracy of the AA consumption test, which, considered overall, represents a competitive alternative to other tubeless tests of pancreatic function.
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PMID:[Amino acid level in plasma--expressed as alpha-amino-nitrogen--reaction to stimulation of the exocrine pancreas: approaches to a new pancreatic function test]. 343 Oct 32


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