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)

We examined the effects of alloxan-diabetes on the kinetic properties of the soluble and the membrane-bound forms of acetylcholinesterase (AChE) in rat brain. The Km (0.15 mM) and Vmax. (1.5 mmol/min per mg of protein) of the soluble form of the enzyme were unchanged in the diabetic animals. The membrane-bound enzyme in the control group displayed a lower Km (0.09 mM) and a higher Vmax. (7.2 mmol/min per mg of protein) compared with the soluble form of the enzyme; the diabetic state caused a significant increase (40%) in both Km and Vmax. Kis values were about 3-4 times higher for the membrane-bound enzyme in both control and diabetic animals. The results suggest that membrane binding and membrane alterations in diabetes can significantly influence the kinetic properties of AChE.
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PMID:Alloxan-diabetes alters kinetic properties of the membrane-bound form, but not of the soluble form, of acetylcholinesterase in rat brain. 774 92

Crude Clostridium histolyticum collagenase was purified by gel filtration and fractionated by anion exchange chromatography into class I with high collagen digestion activity (CDA) and low FALGPA (2-furanacryloyl-L-leucylglycyl-L-prolyl-L-alanine) hydrolysis activity (FHA), class II with low CDA and high FHA, and a fraction called class I/II with intermediate activities. The roles of these collagenase classes in rat pancreatic islet isolation were investigated. Dissociations were carried out with 360 mg of pancreatic tissue in 10 ml of buffer containing 10% (wt/vol) albumin to suppress endogenous proteolytic activity, 100 U of C. histolyticum neutral protease, and one or two purified collagenase(s). For purified nonfractionated (PNF) collagenase, 2.6 mg of enzyme containing 2.4 U CDA and 38.0 U FHA was used, and for the separate classes, comparable amounts of activity were added. PNF collagenase dissociated the tissue completely in 32 min and yielded 5.0 +/- 0.4 microliters islet tissue/g pancreas. Class I collagenase alone dissociated pancreatic tissue extremely slowly and incompletely; only a few islets were released (0.7 +/- 0.2 microliters/g pancreas). Class II collagenase alone dissociated the tissue adequately in 50 min, and a high islet yield of 5.7 +/- 0.6 microliters/g was obtained. With class I/II, a similar dissociation time (47 min) and islet yield (5.5 +/- 0.3 microliters/g) were obtained. Combining class I and class II collagenase resulted in a more rapid dissociation (32 min) and a higher islet yield (7.1 +/- 0.8 microliters/g) than that obtained with PNF collagenase (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Feb
PMID:Different roles of class I and class II Clostridium histolyticum collagenase in rat pancreatic islet isolation. 785 45

This review has considered a number of observations obtained from studies of insulin in perfused liver, hepatocytes, transformed liver cells and in vivo and each of the experimental systems offers advantages. The evaluation of insulin effects on component lipid synthesis suggests that overall, lipid synthesis is positively influenced by insulin. Short-term high levels of insulin through stimulation of intracellular degradation of freshly translated apo B and effects on synthesis limit the ability of hepatocytes to form and secrete TRL. The intracellular site of apo B degradation may involve membrane-bound apo B, cytoplasmic apo B and apo B which has entered the ER lumen. How insulin favors intracellular apo B degradation is not known. An area of recent investigation is in insulin-stimulated phosphorylation of intracellular substrates such as IRS-1 which activates insulin specific cellular signaling molecules [245]. Candidate molecules to study insulin action on apo B include IRS-1 and SH2-containing signaling molecules. Insulin dysregulation in carbohydrate metabolism occurs in non-insulin-dependent diabetes mellitus due to an imbalance between insulin sensitivity of tissue and pancreatic insulin secretion (reviewed in Refs. [307,308]). Insulin resistance in the liver results in the inability to suppress hepatic glucose production; in muscle, in impaired glucose uptake and oxidation and in adipose tissue, in the inability to suppress release of free FA. This lack of appropriate sensitivity towards insulin action leads to hyperglycemia which in turn stimulates compensatory insulin secretion by the pancreas leading to hyperinsulinemia. Ultimately, there may be failure of the pancreas to fully compensate, hyperglycemia worsens and diabetes develops. The etiology of insulin resistance is being intensively studied for the primary defect may be over secretion of insulin by the pancreas or tissue insulin resistance and both of these defects may be genetically predetermined. We suggest that, in addition to effects in carbohydrate metabolism, insulin resistance in liver results in the inability of first phase insulin to suppress hepatic TRL production which results in hypertriglyceridemia leading to high levels of plasma FA which accentuate insulin resistance in other target organs. As recently reviewed [17,254] the role of insulin as a stimulator of hepatic lipogenesis and TRL production has been long established. Several lines of evidence support that insulin is stimulatory to the production of hepatic TRL in vivo. First, population based studies support a positive relationship between plasma insulin and total TG and VLDL [253]. Second, there is a strong association between chronic hyperinsulinemia and VLDL overproduction [309].(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion. 794 13

Selenium and the selenium-dependent glutathione peroxidase (GSH-Px) were measured in healthy and diabetic children from Germany and Hungary. Hyperglycemia and hyperlipidemia are present in diabetes mellitus and they are associated with increased lipid peroxidation. The selenium content of erythrocytes, whole blood and plasma, as well as of plasma glutathione peroxidase activity, were found to be low in the healthy Hungarian children compared to the healthy Germans. Both groups of diabetics had significantly higher blood selenium (1.05 +/- 0.14 versus 0.86 +/- 0.1 mumol/L in Hungarians, 1.34 +/- 0.21 versus 1.12 +/- 0.22 mumol/L in Germans) and higher plasma selenium (0.89 +/- 0.15 versus 0.68 +/- 0.01 mumol/L in Hungarians and 1.01 +/- 0.2 versus 0.88 +/- 0.19 mumol/L in Germans) than the healthy children of the same countries. In all diabetic children the plasma glutathione peroxidase activity and triglycerides were higher and the plasma HDL-cholesterols (HDLC = high density lipoprotein-cholesterol) lower than those in healthy controls. The patients showed linear correlations between blood glucose and plasma glutathione peroxidase activity, as well as in erythrocyte glutathione peroxidase activity with triglycerides (TG) and an inverse correlation with HDL-cholesterol. Plasma selenium correlated only in healthy children with triglycerides, cholesterol and HDL-cholesterol. Irrespective of the geographical region diabetics had a higher selenium status than healthy children. In addition, we found correlations between selenium and lipoproteins in the reference group. The mode of glycation, oxidative procedures and the selenium binding to lipoproteins could explain the different associations in the healthy and diabetic children.
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PMID:Selenium status and lipoproteins in healthy and diabetic children. 801 49

Incubation of cultured rat aortic smooth muscle cells (ASMCs) in a medium containing high glucose concentrations (25 mM) did not affect the basal cytosolic free calcium ([Ca2+]i) but led to significant reductions in peak [Ca2+]i response evoked by arginine vasopressin, angiotensin II, and endothelin-1 (ET-1). This was observed in both the presence and absence of extracellular Ca2+. Maintenance of rat ASMCs in a medium containing mannose (an osmotic control for high glucose) did not affect either the basal or peptide agonist-evoked increase in [Ca2+]i. However, pretreatment with either the nonselective protein kinase C (PKC) inhibitor staurosporine or the selective PKC inhibitor 2,6-diamino-N-([1-(1-oxotridecyl)-2 piperidinyl] methyl) hexanamide reversed the attenuating effect of high glucose on peak [Ca2+]i response evoked by ET-1. Also, short-term incubation of ASMCs with the active phorbol ester, phorbol 12-myristate 13-acetate, led to a reduction in peak [Ca2+]i response to all three agonists, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, which does not activate PKC, had no such effect. Although high-glucose treatment of rat ASMCs led to significant reductions in the maximal number of binding sites to the extent of 39% of [125I]ET-1 specific binding, no significant differences in the affinity (Kd approximately 110 pM) characteristics were evident between control and high-glucose treatment groups. It is proposed that incubation of rat ASMCs with high glucose enhances the de novo synthesis of diacylglycerol and activates membrane-bound PKC and that this, in turn, impairs agonist-mediated intracellular Ca2+ mobilization.
Diabetes 1994 Aug
PMID:High glucose attenuates peptide agonist-evoked increases in cytosolic free [Ca2+] in rat aortic smooth muscle cells. 803 97

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease whose onset is believed to be triggered by unknown environmental factors acting on a predisposing genetic background. Islet-infiltrating T (IIT) cells from two IDDM patients, who had died at the onset of the disease from brain swelling as a complication of ketoacidosis, were analysed. The results provided evidence for the involvement of a pancreatic islet cell membrane-bound superantigen as a diabetes aetiopathogenetic factor. There was a selective expansion of a T-cell receptor (TCR) variable segment of the beta-chain (V beta 7) in these IIT cells in association with unselected V alpha-chain segments; extensive junctional diversity of the TCR V beta 7 chains; and evidence of positive selection, after exposure to diabetic islet cell membrane preparations, of V beta 7+ T-cell clones among peripheral blood lymphocytes from non-diabetic individuals.
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PMID:Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. 809 Jan 94

Coronary heart disease (CHD) is still relatively uncommon in the black population of South Africa. We embarked on a study to determine the prevalence of risk factors leading to CHD in the black population of Durban. The study sample was selected from patients attending a dental clinic at a hospital. A total of 458 Zulus (age range 16-69 years) were studied. The prevalence of CHD was 2.4%. The prevalence percentage of selected risk factors were: hypertension (SBP > or = 140 mmHg and/or a DBP > or = 90 mmHg) was 28%, males 31.9%, females 25.4%; protective levels of high density lipoprotein cholesterol/total cholesterol (HDLC/TC) (> or = 20%) were 81.3%; diabetes, males 4.9%, females 2.9%; smoking > or = ten cigarettes per day, males 28.1%, females 3.4%; obesity, males 3.7%, females 22.6%. We have found the Minnesota Coding System for ECG changes of CHD and Rose questionnaire to be unreliable for eliciting CHD in Blacks. Hypercholesterolaemia is less common and this may explain the low incidence of CHD in Blacks. Epidemics of CHD as seen in the Indian, 'mixed' and white South Africans can still be prevented in the black population but preventive measures must be instituted rapidly.
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PMID:Study of risk factors leading to coronary heart disease in urban Zulus. 811 40

A substantial disturbance of the metabolism of the n-6 essential fatty acids (EFAs) exists in both human and experimental diabetes mellitus. The process of conversion of dietary linoleic acid to gammalinolenic, dihomogammalinolenic and arachidonic acids, and other polyunsaturates is inadequate in diabetic patients. Disturbances of these EFAs and the 1- and 2-series prostaglandins derived from them cause a variety of microvascular, haemorheological, and other abnormalities leading to reduced blood flow and neural hypoxia. This will in turn produce an escalating cycle of further hypoxia through the generation of oxygen-free radicals and aggravation of neural capillary endothelial damage. Endoneurial hypoxia impairs axonal transport, produces demyelination, and reduces neural ATP-ase activity. Furthermore, depletion of polyunsaturated fatty acids derived from n-6 pathway may lead to abnormalities of myelin turnover, membrane-bound proteins (such as enzymes and receptors) and other axonal structural abnormalities. The disorders postulated here may synergistically interact with the metabolic changes described in both the glycosylation and the myoinositol hypotheses and may have important implications in the approach to treat diabetic neuropathy.
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PMID:The use of gamma linolenic acid in the prevention and treatment of diabetic neuropathy. 820 Jan 97

Diabetes mellitus alters the cellular production of eicosanoids in a number of tissues, including the kidney, and these agents have in turn been implicated in the pathogenesis of diabetic nephropathy. As delineated in the streptozotocin diabetic rat (SDR) model, a preferential enhancement of glomerular synthesis of the vasodilatory prostaglandins (PGs) PGE2 and PGI2 with concurrent smaller increases in thromboxane (TX)A2 occurs within 1 week after induction of diabetes. This early alteration in glomerular synthesis of eicosanoids in the SDR has been linked to glucose-induced activation of the glomerular protein kinase C signalling system that enhances phospholipase A2 activity and, therefore, release of membrane-bound arachidonic acid for oxygenation. The preferential increase in glomerular production of vasodilatory PGs may contribute to the glomerular hyperfiltration that is characteristic of early diabetes. After more prolonged (months) diabetes in the SDR, glomerular generation and urinary excretion of thromboxane (TX) are preferentially enhanced. Studies with selective inhibitors of TX synthesis in the SDR have implicated this eicosanoid in the pathogenesis of both albuminuria and glomerular structural changes (basement membrane thickening and mesangial matrix expansion). Direct stimulation of matrix protein production has been demonstrated in cultured mesangial cells in response to both TX and high ambient concentrations of glucose. The actions of TX and glucose on mesangial cell matrix production appear to be interactive, with each signalled through distinct pathways of protein kinase C activation.
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PMID:Eicosanoids in the pathogenesis of the functional and structural alterations of the kidney in diabetes. 823 21

The smaller form of the autoantigen glutamic acid decarboxylase, GAD65 (formerly the 64,000 M(r) autoantigen), is a major target of humoral autoimmunity in type I diabetes. Human autoantisera have been used extensively to characterize the GAD65 antigen in both rat and human islets, but the protein has escaped detection in mouse islets. We have now analyzed the expression of GAD65 and GAD67, the larger glutamic acid decarboxylase protein, in human, rat, and mouse islets of Langerhans and brain, using human monoclonal islet cell autoantibodies, human autoantisera, and experimentally raised antibodies to glutamic acid decarboxylase. Human monoclonal autoantibodies and experimentally raised antibodies reacted with mouse GAD65 produced in a baculovirus expression system by Western blotting and immunoprecipitation and with GAD65 in mouse brain by immunohistochemistry but failed to detect GAD65 in mouse islets by the latter two methods. However, analysis of mouse islets by Western blotting technique, using the most sensitive experimentally raised antibody, showed that mouse islets express both GAD65 and GAD67 but at levels that are severalfold lower than those in mouse brain or in human and rat islets. Furthermore, both human and rat islets predominantly express GAD65, whereas GAD67 is the major glutamic acid decarboxylase protein in mouse islets. Human islets are significantly distinct from mouse and rat islets and from brain because they only express GAD65, which is consistent with the predominant role of this form as a target of autoantibodies associated with beta-cell destruction in humans. Human as well as rat islet GAD65 are found in both membrane-bound and soluble forms. The low level of glutamic acid decarboxylase expression in mouse islets compared with human and rat islets is likely to have implications for both the development of tolerance to glutamic acid decarboxylase as well as the homing of glutamic acid decarboxylase-specific lymphocytes to the mouse beta-cell. In this context, the results suggest 1) that the mouse is ideal for studies of the consequences of an expression of high levels of glutamic acid decarboxylase in the beta-cell from a transgene and 2) that the rat may be better suited than the mouse for development of nontransgenic animal models of glutamic acid decarboxylase autoimmunity by immunization.
Diabetes 1993 Dec
PMID:Differential expression of GAD65 and GAD67 in human, rat, and mouse pancreatic islets. 824 26


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