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)

Dogs fed galactose develop diabetes-like ocular complications that include keratopathy, cataracts, and retinopathy. The purpose of this study was to investigate whether galactosemic dogs display reduced aqueous flow similar to that observed in patients with insulin-dependent diabetes mellitus. Twelve male beagles at 9 months of age were divided into three groups of four. The Galactose group was fed diet containing 30% galactose for 97 months and the Reversal group was fed the galactose diet for an initial 38 months then standard dog diet for the remaining period. The Control group was fed standard dog diet for 97 months. Aqueous flow was determined by fluorophotometry in one eye per dog at 96 and 97 months after the initiation of galactose feeding. Intraocular pressure (IOP) was measured once in the morning by pneumatonometry. Anterior chamber depth was measured by A-scan. At the end of the experiment, eyes were enucleated and processed for histological examination. Dogs fed galactose diet for 97 months had significantly (p<0.05) increased body weights but similar IOP and anterior chamber depth compared to the other groups, and significantly (p=0.05) reduced aqueous flow compared to the control group (4.4+/-2.2 vs. 6.8+/-2.4 microl/min, mean+/-standard deviation, respectively). Additionally, aqueous flow decreased in the Reversal group to 3.1+/-1.3 microl/min (p=0.002). This decrease correlated with morphological changes of the ciliary processes. Like patients with insulin-dependent diabetes mellitus, galactose-fed dogs demonstrate reduced aqueous flow. This reduction was irreversible and independent of the retinopathy present. This animal model may be useful for the study of aqueous humor dynamics in diabetes.
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PMID:Aqueous flow in galactose-fed dogs. 1679 6

Consumption of fish rich in n-3 highly unsaturated FAs (i.e., EPA and DHA) has been suggested to decrease the risk of lifestyle-related diseases such as coronary heart disease, cancer, diabetes, and dementia. Blood levels of those FA are known appropriate biomarkers of both the corresponding dietary FA intakes and fish consumption. In place of traditional handwork methods for extracting FA, we performed an accelerated solvent extraction (ASE) for at least 13 selected FA in plasma and erythrocytes to measure them by GLC. The FA levels (concentrations and compositions) in 35-50 microL of plasma or erythrocytes were extracted by ASE and measured by GLC. Intra- and interassay coefficients of variation were < or = 6.0% for both blood materials, except with a minor group of FA (< or = 1.0% of total FA). When ASE was compared with two traditional handwork methods, FA levels in plasma from 18 healthy subjects were all coincident with very high Pearson's correlation coefficients for the three sets of the same 18 samples (r > or = 0.85 to 0.95, P < 0.0001), except for 18:0 (r = 0.59, P < 0.01). Using ASE and GLC, we have developed a new method for determination the levels of FA in plasma and erythrocytes as biomarkers for dietary intake of fish, fat, and FA. This new method makes it feasible to measure small volumes of samples, automatically, quantitatively, routinely, easily, rapidly and cheaply, with acceptable precision and accuracy.
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PMID:Accelerated solvent extraction for quantitative measurement of fatty acids in plasma and erythrocytes. 1698 38

Inflammation plays an important role in health and disease. Most of the chronic diseases of modern society, including cancer, diabetes, heart disease, arthritis, Alzheimer's disease, etc. have inflammatory component. At the same time, the link between diet and disease is also being recognized. Amongst dietary constituents, fat has gained most recognition in affecting health. Saturated and trans fatty acids have been implicated in obesity, heart disease, diabetes and cancer while polyunsaturated fatty acids (PUFAs) generally have a positive effect on health. The PUFAs of omega-3 and omega-6 series play a significant role in health and disease by generating potent modulatory molecules for inflammatory responses, including eicosanoids (prostaglandins, and leukotrienes), and cytokines (interleukins) and affecting the gene expression of various bioactive molecules. Gamma linolenic acid (GLA, all cis 6, 9, 12-Octadecatrienoic acid, C18:3, n-6), is produced in the body from linoleic acid (all cis 6,9-octadecadienoic acid), an essential fatty acid of omega-6 series by the enzyme delta-6-desaturase. Preformed GLA is present in trace amounts in green leafy vegetables and in nuts. The most significant source of GLA for infants is breast milk. GLA is further metabolized to dihomogamma linlenic acid (DGLA) which undergoes oxidative metabolism by cyclooxygenases and lipoxygenases to produce anti-inflammatory eicosanoids (prostaglandins of series 1 and leukotrienes of series 3). GLA and its metabolites also affect expression of various genes where by regulating the levels of gene products including matrix proteins. These gene products play a significant role in immune functions and also in cell death (apoptosis). The present review will emphasize the role of GLA in modulating inflammatory response, and hence its potential applications as an anti-inflammatory nutrient or adjuvant.
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PMID:Gamma linolenic acid: an antiinflammatory omega-6 fatty acid. 1716 69

Secondary active glucose transport occurs by at least four members of the SLC5 gene family. This review considers the structure and function of two premier members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and renal glucose reabsorption. Genetics disorders of SGLTs include Glucose-Galactose Malabsorption, and Familial Renal Glucosuria. SGLT1 plays a central role in Oral Rehydration Therapy used so effectively to treat secretory diarrhoea such as cholera. Increasing attention is being focused on SGLTs as drug targets for the therapy of diabetes.
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PMID:Active sugar transport in health and disease. 1722 66

Fetuin A and matrix GLA protein--MGP are known as extraosseus calcification inhibitors. The aim of the study was to assess the dependence between metabolic status and fetuin A and matrix GLA protein levels in type 1 diabetic patients without ischaemic heart disease. The study was performed in a group consisting of 35 patients with type 1 diabetes mellitus (22 women and 13 men). Mean age of the studied group equaled 38.8 +/- 11.24 years, duration of diabetes mellitus 20.77 +/- 10.11 years. Fetuin A significantly correlated with HDL-cholesterol (r = 0.45; p = 0.007). Total cholesterol, LDL-chol and triglicerides correlated with HbA1c (r = 0.40, p = 0.03; r = 0.41, p = 0.03 and r = 0.37, p = 0.05), HDL-chol significantly correlated with glucose level at the examination day (r = 0.52, p = 0.04). There were also positive correlations of trigliceride with uric acid (r = 0.47, p = 0.09) and cystatin C (r = 0.44, p = 0.02). There were no correlation of MGP with other examined parameters. Initial results of fetuin A and MGP levels in long-term type 1 diabetic patients without ischaemic heart disease draws attention to new parameters in macroangiopathy development.
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PMID:[Fetuin A and matrix GLA protein in long standing type I diabetic patients without ischaemic heart disease]. 1764 33

Dysmetabolic state in diabetes may lead to augmented synthesis of extracellular matrix (ECM) proteins. In the endothelial cells, we have previously demonstrated that glucose-induced fibronectin (FN) production and that of its splice variant, EDB(+)FN, is regulated by protein kinase B (PKB, also known as Akt). In this study, we investigated the role of Akt1 in ECM protein production in the organs affected by chronic diabetic complications. We studied Akt1/PKBalpha knockout mice and wild-type control littermates. To avoid confounding effects of systemic insulin, we used 30% galactose feeding to induce hyperhexosemia for 8 wk starting at 6 wk of age. We investigated FN mRNA, EDB(+)FN mRNA, and transforming growth factor (TGF)-beta mRNA expression, Akt phosphorylation, Akt kinase activity, and NF-kappaB and AP-1 activation in the retina, heart, and kidney. Renal and cardiac tissues were histologically examined. Galactose feeding caused significant upregulation of FN, EDB(+)FN, and TGF-beta in all tissues. FN protein levels paralleled mRNA. Such upregulation were prevented in Akt1-deficient galactose-fed mice. Galactose feeding caused ECM protein deposition in the glomeruli and in the myocardium, which was prevented in the Akt knockout mice. NF-kappaB and AP-1 activation was pronounced in galactose-fed wild-type mice and prevented in the galactose-fed Akt1/PKBalpha-deficient group. In the retina and kidney, Ser473 was the predominant site for Akt phosphorylation, whereas in the heart it was Thr308. Parallel experiment in streptozotocin-induced diabetic animals showed similar results. The data from this study indicate that hyperhexosemia-induced Akt/PKB activation may be an important mechanism leading to NF-kappaB and AP-1 activation and increased ECM protein synthesis in the organs affected by chronic diabetic complications.
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PMID:Akt activation and augmented fibronectin production in hyperhexosemia. 1766 88

Blood galactose clearance after an intravenous galactose load has been widely used as a quantitative liver function test. We have developed a novel quantitative rat liver function test, the galactose single point (GSP) method, to assess residual liver function with various injuries by measuring single time point galactose concentration in blood after an intravenous bolus injection of galactose. The goal of this study was to evaluate the influence of nonhepatic factors such as hyperglycemia on GSP and galactose elimination capacity (GEC) in rats. Four groups of animal studies were carried out, as follows: (1) normal control (NC), (2) streptozotocin-induced diabetes (DM), (3) carbon tetrachloride-induced hepatotoxicity (CCl(4)), and (4) streptozotocin-induced diabetes with CCl(4)-induced hepatotoxicity (DM + CCl(4)). The serum glucose levels in the diabetic groups (DM and DM + CCl(4)) were significantly increased compared with the NC and CCl(4) groups (P < .001). A significant increase in hepatic activities of aspartate aminotransferase and alanine aminotransferase was observed in the CCl(4)-treated groups (CCl(4) and DM + CCl(4)) compared with the NC and DM groups (P < .001). In comparison with the NC group, the values of GSP and GEC in the diabetic groups (DM and DM + CCl(4)) were significantly reduced (P < .001) and increased (P < .01), respectively. Galactose single point had highly significant correlations with GEC (P < .001). These results suggest that galactose metabolism tests-as quantitative parameters of liver function-should be interpreted with caution in the condition of a significant hyperglycemia.
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PMID:Effects of hyperglycemia on quantitative liver functions by the galactose load test in diabetic rats. 1769 71

Aortic stiffening and aortic calcification are risk factors for cardiovascular events in hemodialysis (HD) patients, and these 2 risk factors are interrelated. Sevelamer decreases aortic calcification but its effect on aortic stiffness has not been investigated previously. Thirteen HD patients commencing sevelamer treatment and 13 matched controls were followed for 11 months. Aortic pulse wave velocity (PWV), augmentation index (AIx), and levels of inhibitors of vascular calcification (fetuin-A, matrix-GLA-protein, osteoprotegerin/RANKL) were measured at baseline and at the end of follow-up, and the differences between the groups were compared. Determinants of the changes in PWV during follow-up were assessed by multivariate linear regression. At baseline, PWV was 9.93 (2.10) m/s in sevelamer-treated patients and 9.20 (2.84) m/s in control patients (p=0.464). By the end of follow-up, PWV decreased by 0.83 (2.3) m/s in sevelamer-treated patients while it increased by 0.93 (1.88) m/s in controls (p=0.042). The direction of changes in AIx were similar, but not statistically significant. There were no significant differences in the levels of inhibitors of calcification either at baseline or during follow-up. In multivariate linear regression sevelamer treatment, diabetes, heart rate, and C-reactive protein were related to the change in PWV. These data suggest that sevelamer treatment is associated with an improvement in aortic stiffness in HD patients, but it does not seem to affect serum levels of inhibitors of vascular calcification.
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PMID:Effect of sevelamer on aortic pulse wave velocity in patients on hemodialysis: a prospective observational study. 1789 5

The C7N-cyclitol containing alpha-glucosidase inhibitor acarbose is commercially produced using developed strains of Actinoplanes and is used in the treatment of patients suffering from diabetes type II. We have identified a second acarbose production cluster using a genomic cosmid gene bank from Streptomyces glaucescens GLA.O and sequenced a region (42658bp; accession AM409314) which clearly contained a gene cluster (gac-cluster) for the synthesis of acarbose or acarbose related endproducts. The gac-cluster exhibited large similarities to the acb-gene cluster from Actinoplanes. However, remarkable differences are found in the biosynthesis of the C7N-cyclitol in the two acarbose biosynthesis pathways. We show the expression of selected genes using RT-PCR approaches, we were able to detect small amounts of acarbose or acarbose related metabolites and we have characterized the GacK protein, an acarbose kinase, which specifically phosphorylates acarbose and acarbose homologs. All these data in combination with the postulated functions of the encoded Gac proteins clearly indicate that also in S. glaucescens a recycling mechanism for acarbose ("carbophor") which had been described for the first time for acarbose cluster from Actinoplanes, is also realised.
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PMID:The gac-gene cluster for the production of acarbose from Streptomyces glaucescens GLA.O: identification, isolation and characterization. 1905 89

Treatment of gastropod mollusks of pond snail Lymnaea stagnalis and orb snail Coretus corneus with streptozotocin was followed by an increase in hexose content in the hemolymph and development of the diabetic state (day 1 after treatment). Functional activity of the hormone-sensitive adenylate cyclase system significantly decreased in the muscles and hepatopancreas of mollusks with diabetes. We revealed a decrease in the regulatory effects of biogenic amines and peptide hormones that were realized via stimulatory (octopamine, dopamine, serotonin, tryptamine, and relaxin) and inhibitory G proteins (somatostatin). Disturbances in the hepatopancreas were more pronounced than in the muscle. The severity of disorders in the adenylate cyclase system reached maximum 1 day after streptozotocin treatment. The sensitivity of this system to hormonal and nonhormonal agents was partially restored on days 3 and 5. Hexose content in the hemolymph was elevated after streptozotocin treatment, but returned to normal on day 3. Our results indicate that hyperglycemia is one of the key factors for dysfunction of the adenylate cyclase system in mollusks with the diabetic state.
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PMID:Variations in functional activity of the hormone-sensitive adenylate cyclase system in tissues of gastropod mollusks with streptozotocin-induced diabetes. 1948 11


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