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

The activity of all principal groups of lysosomal enzymes (acid phosphatase, lipase, beta-galactosidase, sulphatase and cathepsin B) was measured in the visual cortex of rabbits with experimental diabetes. In the first stage of diabetes (21 days), it was observed that enzyme activities in the free fraction and in the membrane-bound fraction are decreased as compared to the initial values determined in healthy animals. In the later stages of diabetes (90-180 days), all lysosomal enzyme activities increased except for sulphatase. This indicated a superiority of catabolic processes in visual cortex cells in the course of experimental diabetes.
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PMID:The activity of lysosomal enzymes in visual cortex of rabbits during experimental diabetes. 870 84

Genetic hepatic lipase (HL) deficiency is associated with low density lipoprotein (LDL) rich in triglycerides (TG), whose affinity for B:E receptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human insulin-dependent Diabetes Mellitus (IDDM), HL activity and the characteristics of LDL have not been studied. The objective of our study is to evaluate the relation between HL activity and the chemical composition of LDL in treated IDDM patients. Subjects were 15 IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The IDDM patients were classified by the WHO criteria, were free of nephropathy and hypothyroidism, and received no medication except insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The IDDM group was divided into two subgroups: subgroup IDDM-A (n = 9) with HL values > or = 4.3 and IDDM-B (n = 6) with HL < or = than 4.2 mumoles glycerol/ml h. the HL in IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood samples were drawn after 12 h fasting. Percentage of HbA1c and plasma concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and TG were assayed. LDL was separated by sequential ultracentrifugation at densities of 1.019-1.063 g/ml and its chemical composition was analyzed. The most relevant results were: plasma TG concentration was higher in IDDM than in C (p < 0.05) (Table 2), although average values DMID not exceed the reference values of 200 mg/dl. The TG-LDL were higher in IDDM than in C: 24.8 +/- 2.7 vs 17.5 +/- 1.1 mg/dl plasma, media +/- SE, (p < 0.02). This difference reflected the values of IDDM-B, whose plasma concentrations of TG-LDL were higher than in C: 32.3 +/- 3.6 vs 17.5 +/- 1.1 mg/dl (p < 0.001), and also higher than in IDDM-A (p < 0.02). (Table 3). The chemical composition of LDL in IDDM-B contained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3% (p < 0.05), a lower percentage of cholesterol than IDDM-A: 39.0 +/- 1.7 vs 45.2 +/- 2.2% (p < 0.05) and also a larger percentage of proteins than IDDM-A: 28.9 +/- 1.9 vs 20.8 +/- 1.0% (p < 0.01). The correlations between TG/cholesterol and HL activity in IDDM were r = -0.53 (p < 0.05) and in IDDM-B, r = -0.81 (p = 0.05). The noteworthy result of this study is the modification of the LDL particle in IDDM, rich in TG in patients with low HL activity. Anomalies in the chemical composition of LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated that LDL is an indisoluble association of lipids and apoproteins, and that both act simultaneously to hold the apoB in a spatial position that expresses normal epitopes. It has been described that particles of LDL rich in TG and poor in cholesterol, shows low affinity for LDL receptors in human fibroblasts. Also in IDDM the interaction of LDL rich in TG with B:E receptors is decreased. This might be one more mechanism contributing to the accelerated atherosclerosis of these patients. Our results suggest that there may be a threshold of HL activity for the complete hydrolysis of the TG of LDL, for the normalization of the TG/cholesterol relation and for the conformation of typical LDL particles.
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PMID:[Low density lipoprotein rich in triglycerides and hepatic lipase activity in insulin-dependent diabetic patients]. 872 71

Pancreatic amylase and lipase activities were measured in sera of 307 Caucasian insulin-dependent diabetes mellitus patients (IDDM) at clinical onset, 303 nondiabetic siblings of registered patients, and 207 control subjects under age 40 years. In all subject groups lipasemia and pancreatic (but not salivary) amylasemia increased with age and were significantly correlated. Using age-dependent reference ranges, reduced pancreatic enzyme levels were measured in 18% of patients, 6% of siblings, and only 2% of control subjects (p < 0.001). Increased lipase levels were noted in 10% of patients and in only 3% of siblings and 2% of control subjects (p < 0.001). Using both univariate and multivariate statistical analysis, elevated lipase activities at clinical onset were associated with higher titers of autoantibodies against islet cell cytoplasmic antigens and glucagon, but not against insulin or the 65-kDa isoform of glutamic acid decarboxylase (GAD65-Ab), or with markers of genetic predisposition or metabolic dysregulation. These findings indicate the presence of modest, but statistically significant, variations in circulating pancreatic enzyme levels in 28% of IDDM patients at clinical onset (p < 0.001 vs. 5% in control subjects). Increased lipase levels may express a form or a stage of the disease with exocrine cell damage; their association with higher titers of islet cell and glucagon autoantibodies is not yet explained. Lower lipase and isoamylase levels are thought to result from the reduced acinar cell function in the vicinity of insulin-depleted islets. It must be tested whether pancreatic enzyme activities in serum can also be altered during the preclinical stage and can thus be considered as an additional marker for the disease process in the pancreas.
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PMID:Abnormal circulating pancreatic enzyme activities in more than twenty-five percent of recent-onset insulin-dependent diabetic patients: association of hyperlipasemia with high-titer islet cell antibodies. Belgian Diabetes Registry. 874 Mar 97

In order to gain a better understanding of the kinetics of activation and inhibition of hepatic monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) by fatty acid, we examined the effect of fatty acid with respect to MGAT's long-chain acyl-CoA substrate in Triton X-100 mixed micelles. At concentrations between 2.5 and 5.3 mol %, oleic acid stimulated MGAT activity 2-fold, whereas oleic acid inhibited MGAT at concentrations higher than 7.5 mol %. The dependence on palmitoyl-CoA was highly cooperative with a Hill constant of greater than 2.4. When present at less than 3 mol%, oleic acid eliminated the lag in the dependence curve. When concentrations of oleic acid were higher than 3 mol %, Michaelis-Menton kinetics were observed with an apparent k(m) value of about 54 microM for palmitoyl-CoA but with progressively decreasing Vmax values. This effect was not observed with octanoic acid, suggesting that the medium-chain fatty acid is unable to associate stably with the mixed micelle and, thus, cannot substantially alter substrate affinity. When anionic phospholipids were tested, phosphatidic acid, lysophosphatidic acid, phosphatidylserine, and phosphatidylinositol eliminated some of the lag in activation by palmitoyl-CoA. At high molar concentrations of the anionic lipid activators, apparent k(m) values ranged from 77 microM for phosphatidic acid to 196 microM for phosphatidylinositol. Zwitterionic phospholipids had no effect, nor did the non-phospholipid activators bovine serum albumin or sn-1,2-diacylglycerol. CaCl2, but not neomycin or KC1, could overcome the inhibitory effect of oleic acid; thus, the inhibitory effect of fatty acid did not appear to occur by electrostatic interactions. These blockers did not change the effects observed with the anionic phospholipid activators or with the inhibitor, sphingosine. An altered k(m) for palmitoyl-CoA in the presence of fatty acid or anionic phospholipid suggests that both long-chain fatty acids and phospholipid cofactors may induce a conformational change in MGAT, thereby altering the enzyme's affinity for its long-chain acyl-CoA substrate. These data further support the hypothesis that the synthesis of glycerolipids via the monoacylglycerol pathway may be highly regulated via a variety of lipid second messengers such as phosphatidic acid and diacylglycerol, as well as by the influx of fatty acids derived from high-fat diets, or from the hydrolysis of adipocyte triacylglycerol during fasting or diabetes.
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PMID:Fatty acids and anionic phospholipids alter the palmitoyl coenzyme A kinetics of hepatic monoacylglycerol acyltransferase in Triton X-100 mixed micelles. 875 39

In an effort to evaluate the effectiveness of islet transplantation in correcting exocrine dysfunction, young male Lewis rats were made diabetic by i.v. streptozotocin injection. Diabetes status was confirmed by decrease in insulin and increase in blood glucose and glycosylated hemoglobin levels. Pancreatic islets were isolated from age-matched control syngeneic rats by collagenase digestion followed by purification through a Ficoll gradient. Islets (approximately 1200) were grafted to the liver by intraportal injection to animals at 8 weeks after diabetes was established. Transplanted rats were sacrificed 4 weeks after correction of hyperglycemia. Diabetes resulted in decrease in body weight. Transplantation reversed the body weight loss and led to a body weight gain. Diabetes resulted in a decrease in pancreatic amylase (1.4 +/- 0.4 U/mg protein compared with a control value of 121.9 +/- 3.2 U/mg protein) and a slight increase in lipase (87.3 +/- 5.5 U/mg protein compared with a control value of 69 +/- 4.7 U/mg protein). Transplantation completely normalized amylase (132.2 +/- 25.0 U/mg protein) and lipase (56.3 +/- 3.9 U/mg protein) in spite of an imperfect correction of blood insulin, glucose, and glycosylated haemoglobin levels in these rats. These data demonstrated that islet transplantation is very effective in correcting the exocrine enzyme changes resulting from diabetes. Evaluation of steady-state levels of amylase mRNA in these groups of animals by Northern blots showed a decrease in the amylase mRNA level in diabetes and a return to that of control in transplanted rats, indicating that the control of amylase expression is most likely at the pretranslational level.
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PMID:Normalization of pancreatic exocrine enzymes by islet transplantation in diabetic rats. 882 73

Clinical as well as experimental studies in insulinopenic diabetes mellitus have demonstrated abnormal pancreatic exocrine responses to cholecystokinin (CCK). In the present study, we examined pancreatic exocrine and endocrine function in the recently developed genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared them with those in the control Long-Evans Tokushima Otsuka (LETO) rats of the same age. Stepwise increasing doses of CCK octapeptide (CCK-8; 0.027-7.0 nmol.kg-1.h-1) evoked a characteristic biphasic dose-response curve for pancreatic juice and protein output in the LETO rats, whereas the OLETF rats were totally insensitive to CCK-8 stimulation. However, the responsiveness and the sensitivity to both carbamylcholine and secretin were similar in the two groups. Intraduodenal infusion of casein (500 mg/h) failed to stimulate pancreatic exocrine secretion in the OLETF rats despite a greater CCK response than in the LETO rats (peak response: 8.43 +/- 0.97 vs 5.12 +/- 0.30 pmol/l in LETO, P < 0.01). Intravenous infusion of CCK-8 (4.4 nmol.kg-1.20 min-1) caused a significant increase in serum insulin concentrations and a concomitant decrease in glucose levels in the LETO rats but not in the OLETF rats. On the other hand, an intravenous bolus injection of 1.1 mmol/kg glucose caused a greater insulin release in the OLETF rats than in the LETO rats. In contrast, gastric acid secretion in the OLETF rats was significantly high in basal and in response to intravenous infusion of CCK-8 compared with that in the LETO rats. Four subcutaneous injections of 20 micrograms/kg caerulein at hourly intervals over 3 h induced acute pancreatitis in the LETO rats but did not elicit any significant increase in serum amylase or lipase activities and pancreatic wet weight or histological evidence of acute pancreatitis in the OLETF rats. These results indicate that the exocrine and endocrine pancreas of the recently developed genetically diabetic OLETF rats are totally and specifically insensitive to exogenous and endogenous CCK stimulation, whereas parietal cells in these rats are sensitive to CCK stimulation.
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PMID:Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats. 892 5

alpha 2-macroglobulin-trypsin complexlike substance (MTLS) was determined in plasma of pancreatic and nonpancreatic diseases using a two-step enzyme immunoassay to study the diagnostic and pathophysiological significance of MTLS. Plasma levels of MTLS in acute pancreatitis (mean +/- SD = 265.6 +/- 346.2 ng/ ml, n = 9), calcified chronic pancreatitis (128.6 +/- 257.4, n = 13), and noncalcified chronic pancreatitis (13.5 +/- 12.5, n = 10) were significantly higher than that in controls (3.6 +/- 1.8, n = 81). In other diseases such as gastric cancer, hepatoma, diabetes mellitus, and gallstones, MTLS values were not different from those of control. Plasma MTLS values showed low correlation with serum trypsin, elastase 1, pancreatic amylase, lipase, and pancreatic secretory trypsin inhibitor (PSTI). The elevation of plasma MTLS values in acute pancreatitis suggests that plasma MTLS levels reflect that protease is inappropriately activated in pancreatic acinar cell and released into the circulation and that the determination of MTLS can be useful for diagnosis and pathophysiology of acute pancreatitis and chronic pancreatitis.
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PMID:Plasma alpha 2-macroglobulin-trypsin complexlike substance (MTLS) in pancreatic disease. 895 9

The aim was to investigate sulodexide as a possible therapeutic tool for treating micro- and macroalbuminuria in diabetic patients. Fifteen patients (13 micro- and 2 macroalbuminuric) with Type II diabetes, were treated with 600 lipoprotein-lipase releasing units of sulodexide by the intramuscular route, daily for 28 days, and followed up for 2 months. The main evaluation parameter was the albumin excretion rate. At the end of treatment, six of the 13 microalbuminuric patients showed a decrease in the albumin excretion rate, which increased again in three of the six during follow-up. In the two macroalbuminuric patients the albumin excretion rate decreased at the end of treatment and remained unchanged after a further 2 months. Overall analysis (15 patients) showed a significant decrease (P < 0.05) in the albumin excretion rate compared with baseline. Metabolic control and blood pressure remained unchanged during the entire period of study. No adverse events were registered. It is concluded that sulodexide administration has a favourable effect in reducing the albumin excretion rate in Type II diabetic patients with micro- and macroalbuminuria.
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PMID:Glycosaminoglycans as a possible tool for micro- and macroalbuminuria in diabetic patients. A pilot study. 910 Jan 62

In patients with insulin-dependent diabetes mellitus (IDDM), albuminuria reflects widespread vascular dysfunction. Albuminuria has been associated to defects of heparan sulfate proteoglycan (HSPG) within the extracellular matrix. Our hypothesis is that loss of HSPG in vascular walls reduces the HSPG-bound lipoprotein-lipase activity (LPLA), thereby causing elevated levels of plasma triglyceride (TG) seen in IDDM patients with albuminuria. The aim of the present study was to evaluate whether LPLA in muscle capillaries could be related to TG in IDDM patients with and without albuminuria. This is a cross-sectional study including ten healthy control subjects (group C), nine patients with IDDM and urinary albumin excretion rate (AER) of 30 mg/24 h or less (group D0) and 20 patients with IDDM and AER greater than 30 mg/24 h (group DA). Muscle LPLA, plasma TG, total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and very-low-density lipoprotein cholesterol (VLDL) were measured. Between groups no difference in total cholesterol, TG, VLDL, and LDL was found. In patients with albuminuria, LPLA was reduced compared to controls, however, the difference between the groups was not statistically significant [median (range)] 35.9 mU/g (20.4-103) versus 44.6 mU/g (28.2-57.2) and 40.9 mU/g (21.7-53.5) in group DA, C, and D0, respectively, p = 0.76. AER was not correlated to LPLA. An overall negative correlation between TG and LPLA was found; r = -0.33, p = 0.04, supported by an overall significant positive correlation between LPLA and HDL; r = 0.32, p = 0.045. We conclude that, in insulin-dependent diabetes mellitus, skeletal muscle lipoprotein-lipase activity is associated with plasma triglyceride, while an association between lipoprotein-lipase activity and urinary albumin excretion is questionable.
J Diabetes Complications
PMID:Skeletal muscle lipoprotein-lipase activity in insulin-dependent diabetic patients with and without albuminuria. 920

People with non-insulin-dependent diabetes mellitus (NIDDM) have a higher incidence of cardiovascular disease (CVD) than the non-diabetic population. In addition, NIDDM patients have a spectrum of lipid abnormalities that may confer an increased risk of developing CVD. The pattern of dyslipidaemia seen in NIDDM patients is different from that seen in the non-diabetic population. This suggests that patients with NIDDM may need different lipid-lowering treatment from that used in the non-diabetic population. In the post-absorptive state, secretion of very low-density lipoprotein (VLDL) is higher in patients with NIDDM, possibly because of the impaired ability of insulin to inhibit lipolysis and to reduce hepatic VLDL secretion. Clearance of triglyceride-rich lipoproteins is also important in determining the extent of postprandial hyperlipidaemia. Lipoprotein lipase (LPL) reduces plasma lipoprotein concentration via several mechanisms. In patients with NIDDM, the capacity of LPL to minimize postprandial hyperlipidaemia may be reduced, although the pathophysiological basis of this is not known. Other changes in patients with NIDDM, such as modifications to cholesteryl ester transfer protein (CETP) and hepatic lipase activity, may also affect postprandial lipaemia but such effects are probably secondary to alterations in lipoprotein clearance. Present evidence suggests that postprandial hyperlipidaemia is atherogenic. There are, however, little specific data from patients with NIDDM. More studies are therefore needed to establish the optimal treatment of dyslipidaemia in patients with NIDDM.
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PMID:Postprandial lipoproteins in non-insulin-dependent diabetes mellitus. 927 17


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