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

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
Diabetes 1989 Jul
PMID:Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. 273 64

A pilot study to improve unhealthy life habits of thirty middle-aged male clerical workers (45 +/- 3.58 yr.) with mild health disorders such as hypertension, hypercholesterolemia, diabetes mellitus and fatty liver was carried out. Under prohibition of smoking and alcohol intake, they spent five nights and six days at a hot spring resort, taking part in planned health training programs which included aerobic training, hiking in forests, hot spring baths, cooking practice and lectures about healthy life, controlled by medical, dietary and physical training staffs. To evaluate the short-term effects of these activities, body weight, blood pressure, serum lipid (total cholesterol, high-density-lipoprotein cholesterol, triglyceride, total free fatty acid and phospholipid), blood sugar, uric acid, gamma-glutamyl transpeptidase (gamma-GTP) and glutamic-oxaloacetic transaminase (GOT) were examined early in the morning of the second (before) and the fifth (after) days, and then their impressions of these recreation activities were monitored by questionnaires on the sixth day. By t-tests of all before-and-after data, it was shown that mean values of body weight, systolic blood pressure, high-density-lipoprotein cholesterol, triglyceride, phospholipid and gamma-GTP were improved, but fasting blood sugar, uric acid and GOT were not improved. In comparison of blood pressure levels, the hypertensive group (n = 9) showed lowering in both systolic and diastolic blood pressure, though the normal group (n = 10) had slight elevation. In addition, in the hypercholesterolemic group (n = 11, greater than or equal to 220 mg/dl) mean total cholesterol values decreased, conversely in the hypocholesterolemic group (n = 6, less than 180 mg/dl) they increased. Moreover, the obese group (n = 15, obesity index greater than or equal to 120%) showed greater decreases of body weight, triglyceride and phospholipid than the non-obese group. From questionnaires, it was confirmed that through these recreation activities most participants found mental and spiritual satisfaction, in spite of heavy physical loads. The short-term recreation activities under a stressless environment seemed to maintain the function of homeostasis in the body, but further investigation is needed to examine the relation between the contents of diets and physical activities, and to follow the long-term effects on the participants.
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PMID:[A study on the physical effects of short-time recreation activities at a hot spring resort on unhealthy middle-aged workers]. 281 Aug 61

This study investigates the diabetes-induced lesions in liver and kidney and in addition the possible side effects of the diabetogenic substance streptozotocin (SR) on these organs in non-diabetic animals. 5-week-old female Wistar rats were injected 65 or 130 mg SR/kg body mass. Some animals of the drug group did not become hyperglycemic; thus it was possible to separate the drug effect from the diabetic influence on liver and kidney. In serum investigations some metabolic changes concerning the activities of the liver enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and the concentrations of urea and creatinine up to 30 days after drug application were studied. SR in hyperglycemic animals causes a time and dose dependent rise in all investigated parameters. Also in normoglycemic rats a significant increase in alkaline phosphatase and in creatinine was observed after 10 days. After 21 and 30 days there were no differences compared to untreated control rats, whereas elevated levels were observed in the hyperglycemic rats. Thus our results support the view of a short damaging effect of SR on liver and kidney without inducing a diabetic state; in hyperglycemic rats the damaging effect is more pronounced.
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PMID:Effect of streptozotocin on transaminases, creatinine and urea in serum of rats. 297 78

High-performance liquid chromatography analysis of acid-extracted tissues revealed decreases of high-energy nucleotides and increases in low-energy nucleotides and metabolites in heart, diaphragm, and liver but not in kidneys of diabetic rats. In comparison with nondiabetic rats, the total adenine nucleotide content of diabetic rat heart and diaphragm but not liver decreased, indicating an increase in catabolism of AMP. Maximal initial rates of the AMP catabolic enzymes 5'-nucleotidase, adenosine deaminase, and AMP deaminase were elevated in the hearts of BB/Wistar and streptozocin-induced diabetic rats. Nucleotide salvage enzymes adenylosuccinate synthetase and adenylosuccinate lyase were elevated above normal in the diabetic heart, whereas hypoxanthine-guanine phosphoribosyl transferase was not altered. Cytosolic-to-mitochondrial ratios from maximal initial rates after correction for mitochondrial breakage were increased above controls in diabetic hearts for nucleoside diphosphokinase and aspartate aminotransferase. Nucleotide levels, degradation rates, and substrate compartmentation between cytosol and mitochondria are discussed in relation to concurrent diabetes.
Diabetes 1988 May
PMID:Adenine nucleotide metabolism in hearts of diabetic rats. Comparison to diaphragm, liver, and kidney. 336 Feb 19

We compare the clinical features and hospital outcomes in 83 diabetic patients admitted with acute myocardial infarction and 380 nondiabetic patients with levels of glycosylated hemoglobin (HbA1c) low enough to exclude undiagnosed diabetes. The hospital mortality was 42.2% in diabetic and 24.7% in nondiabetic patients, an odds ratio of 2.22 (CI 1.37-3.60, P less than .002). The excess mortality was due to cardiogenic shock and left ventricular failure (pump failure). There was no difference in peak levels of aspartate transaminase between the groups. Among the diabetic patients, the admission levels of plasma glucose and peak levels of aspartate transaminase were higher among those who developed pump failure or died, but there was no relationship between outcome and gender, disease duration, or treatment. Prior blood glucose control, as judged by levels of HbA1c, was not related to hospital outcome (P greater than .5). In a further study, the 83 diabetic patients were compared with 249 age- and sex-matched diabetic subjects without myocardial infarction for treatment, disease duration, and control. There was an increased risk of admission with myocardial infarction of 2.35 (CI 1.41-3.92, P less than .005) within the first 5 yr of diagnosis of diabetes. Infarct patients had significantly lower levels of HbA1c than control subjects (P less than .005), but treatment did not differ between groups. Neither incidence nor case fatality of myocardial infarction in diabetic patients is positively associated with cumulative glycemic exposure.
Diabetes Care 1988 Apr
PMID:Determinants of hospital admission and case fatality in diabetic patients with myocardial infarction. 340 92

Enzyme activity in the livers of mice was studied in examining the metabolic disturbances of diabetes. Spontaneously non-obese diabetic (NOD) mice, mice with alloxan-induced diabetes (Allo), and control ICR mice were used. As NOD mice undergo a spontaneous pathogenic process over time, younger and older NOD mice were compared (non-diabetic and diabetic) as were control ICR mice. Two liver enzymes became more active with age, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). AST activity increased more in the hyperglycemic mice, i.e., the diabetic NOD and the Allo mice, than in the normoglycemic group, i.e., the ICR and non-diabetic NOD mice. Abnormally high AST activity was seen in the cytosolic fraction of the liver but not in the mitochondrial fraction. The changes in enzyme activity in diabetic mice were independent of any age-associated changes. The higher AST levels in diabetic mice are thought to be consistent with their greater need for gluconeogenic substrate. AST showed a more notably higher increase than did ALT in this study, and lactate dehydrogenase showed no significant changes.
Diabetes Res Clin Pract 1988 May 19
PMID:Aminotransferase activity in the liver of diabetic mice. 340 35

The EXPERT consultation system-building tool, a knowledge-based artificial intelligence program developed at Rutgers University, has been applied to the development of a laboratory consultation system facilitating sequential laboratory testing and interpretation. Depending on the results of a basic panel of laboratory tests, the system requests that specific secondary tests be performed. Input of these secondary findings can result in requests for tertiary testing, to complete the database necessary for interpretation. Interpretation of all results is based upon final inferences from the collected findings through a series of rules, a hierarchical network that yields an efficient production system not easily obtained through conventional programming. The rules included in this model are based upon initial results for total protein, calcium, glucose, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, thyroxin, hemoglobin, mean corpuscular volume, and the concentrations of four drugs. Pertinent clinical history items included are jaundice, diabetes, thyroid disease, medications, and ethanol. Implementing this system in a laboratory-based accelerated testing program involving outpatients maximized the effective use of laboratory resources, eliminated useless testing, and provided the patient with low-cost laboratory information.
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PMID:Application of the EXPERT consultation system to accelerated laboratory testing and interpretation. 352 78

The streptozotocin diabetic rat was selected as a model to study how insulin deficiency alters vitamin B6 utilization by focusing on pyridoxal phosphate levels and aspartate aminotransferase activities in liver tissues. Diabetes of 15 weeks' duration lowered plasma pyridoxal phosphate levels by 84%. Normal plasma pyridoxal phosphate was 480 pmole/ml. Fractionation of liver into mitochondrial and extramitochondrial compartments demonstrated that diabetes caused a 43% diminution in mitochondrial pyridoxal phosphate per gram of liver. There was no cytoplasmic change in these diabetic rats. Mitochondrial aspartate aminotransferase activity was decreased 53% per gram of diabetic liver and cytoplasmic aspartate aminotransferase activity was elevated 3.4-fold. Damage to diabetic mitochondria during preparation procedures could not account for the rise in cytoplasmic aspartate aminotransferase activity. Electrophoresis showed that in the diabetic cytoplasm both cathodal and anodal forms of the enzyme were elevated. Speculations concerning mitochondrial loss and cytoplasmic gain of enzyme activity as well as those on the reduction of plasma pyridoxal phosphate in the diabetic rat are presented.
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PMID:Experimental diabetes causes mitochondrial loss and cytoplasmic enrichment of pyridoxal phosphate and aspartate aminotransferase activity. 374 6

Biological intra-individual variation in concentrations of 16 clinical biochemical analytes in serum was estimated for 27 patients with insulin-dependent diabetes mellitus (IDDM), and results were compared with those for apparently healthy individuals. In general, the variation was significantly higher in the patients. The ratio of the average intra-individual variation in IDDM patients to that in normal subjects exceeded 2.0 for Na+, K+, creatinine, and alpha-amylase; 1.50 to 2.0 for Cl-, total protein, albumin, cholesterol, and hemoglobin; and 1.2 to 1.5 for urea, uric acid, high-density-lipoprotein cholesterol, and aspartate aminotransferase. This increased variability in IDDM patients may be caused by variations in osmotic diuresis. Average intra-individual variations were greater for women than for men for Na+, total protein, albumin, and hemoglobin. Individual values showed a gaussian distribution for all analytes, including enzymes and triglycerides. No intra-individual variation was time dependent. For practical purposes, decision-making criteria in monitoring IDDM can be derived from the estimated biological component of intra-individual variation and the analytical variation established for each laboratory.
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PMID:Intra-individual variation of some analytes in serum of patients with insulin-dependent diabetes mellitus. 380 96


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