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)

Arylsulfonylamino acids, displaying a wide range of inhibitory activities versus rat lens aldose reductase (RLAR), were analyzed for enzyme selectivity in several test systems. These RLAR inhibitors were found not to produce significant inhibition of genetically-linked reductases (aldehyde reductase, ALR), catalytically similar reductases (Pachysolen tannophilus xylose reductase, PTXR), functionally distinct oxidoreductases (glutathione reductase, GR, lactate dehydrogenase, LDH, and gamma-transaminase, GABA-T), and thymidylate synthase (TS). These data suggest that aldose reductase differs significantly from other oxidoreductases in its inhibitor binding domain(s). Furthermore, the aldose reductase selectivity demonstrated by the arylsulfonylamino acids suggests that these compounds may not inhibit other key metabolic transformations in various cell types and that they may function as selective probes for studies of the relationship between aldose reductase mediated biochemical changes and the pathologies of chronic diabetes.
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PMID:Enzyme selectivity analyses of arylsulfonylamino acid aldose reductase inhibitors. 750 72

The present case was a 44-year-old man who had been diagnosed as having noninsulin-dependent diabetes mellitus 2 years before admission. He gradually showed severe neuropathy and emaciation because of poor control of his blood glucose levels. He was admitted to our hospital because of disturbance of consciousness with hyponatremia. The endocrinological findings including thyroid and adrenal functions revealed no abnormalities. Insufficiency of water diuresis was noted in the water loading test. Severe orthostatic hypotension was noted during the standing up test, and an excessive response in the plasma ADH level was also noted. These findings demonstrated that excessive ADH secretion occurred to compensate for the fall in blood pressure because of the breakdown of homeostatic regulation in blood pressure due to diabetic neuropathy. It is suggested that hyponatremia seemed to be subsequently induced by hypersecretion of ADH.
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PMID:Possible involvement of hypersecretion of ADH in hyponatremia in a diabetic patient complicated with severe neuropathy. 831 11

Mounting experimental evidence links increased aldose reductase activity with diabetes-related kidney functional changes. To investigate the interrelationship of NADPH-dependent reductases in the human kidney, both aldose reductase and aldehyde reductase were purified from human kidney by a series of chromatographic procedures, including gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A, and chromatofocusing on Mono P. Each purified enzyme appeared as a single band on polyacrylamide gel after electrophoresis or isoelectric focusing. Aldose reductase has a pI of 5.7 and apparent molecular weight of 37 kDa, calculated from SDS-polyacrylamide gel electrophoresis, while aldehyde reductase has a pI of 5.2 and molecular weight of 39 kDa. Similar molecular weights were also obtained by gel filtration, indicating that both aldose and aldehyde reductases are present as monomers in the human kidney. Aldehyde reductase is primarily localized in the cortex, while the medulla contains aldose reductase. Both enzymes displayed properties consistent with the general characteristics of aldose and aldehyde reductases obtained from either rat or dog kidney. Purified aldose reductase utilizes aldose sugars such as D-xylose, D-glucose, and D-galactose as substrates while aldehyde reductase preferentially reduces D-glucuronate and oxidizes L-gulonate to D-glucuronate. Despite the lower apparent affinity of aldehyde reductase for aldose sugars (approximately 20- to 100-fold less) both enzymes reduced D-xylose, D-glucose, and D-galactose to their respective sugar alcohols in in vitro incubation studies where the generated sugar alcohols were identified by gas chromatography. Both enzymes were also inhibited by aldose reductase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
J Diabetes Complications
PMID:Human kidney aldose and aldehyde reductases. 834 12

A 62-year-old male with small cell lung cancer (SCLC) associated with Cushing's syndrome and diabetes insipidus (DI) is reported. The patient was referred to our hospital for treatment of SCLC. A diagnosis of paraneoplastic Cushing's syndrome was made on the basis of an elevated serum ACTH (623.5 pg/ml) level, elevated excretion of urinary 17-OHCS (18.01 mg/day), obesity, hypertension, hyperglycemia, persistent hypokalemia, alkalosis, and no history of diabetes mellitus. He was also diagnosed as having DI based on polyuria and polydipsia, low specific gravity of the urine (1.007-1.010), low serum ADH (1.4 pg/ml) level, normal plasma osmolarity (29 mOsm/kg H2O), and the results of water deprivation test. DI and a left visual field defect was suggestive of metastasis to the pituitary region, but no lesion was detected by either CT scan or MRI scan. The patient failed to show a good response to intensive chemotherapy, and died of the tumor five months after commencing chemotherapy. Post-mortem examination revealed metastases to the hypothalamic-neurohypophyseal region, lungs, liver, adrenal glands, bone, bone marrow, and hilar and mediastinal lymph nodes.
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PMID:[A case of small cell lung cancer associated with diabetes insipidus and Cushing's syndrome]. 839 May 89

Sugar alcohols have been reported to accumulate in retinal pigment epithelium (RPE) of diabetic animals. This finding has raised interest in the role of RPE in diabetes-associated retinal changes such as cystoid macular edema. To confirm the presence of aldose reductase in this tissue, the NADPH-dependent enzyme was purified to an apparent homogeneity from cultured human RPE cells, characterized, and its biochemical properties investigated. The induction of aldose reductase by hypertonic stress was also examined. The purification of aldose reductase was performed by a series of chromatographic steps which include gel filtration, affinity chromatography and chromatofocusing. Final purity achieved was monitored by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The kinetic properties and susceptibility to inhibition of the purified aldose reductase were essentially identical to aldose reductase purified from human placenta and kidney. In addition to aldose reductase, chromatofocusing demonstrated the presence of aldehyde reductase, another NADPH-dependent reductase. However, the amounts of aldehyde reductase present were much smaller than those of aldose reductase and the levels of aldehyde reductase appeared too small to contribute to the polyol production in the RPE cells. Culture of RPE cells in hypertonic medium containing 150 mM sodium chloride (600 mosmol total) increased both reductase activity, monitored with DL-glyceraldehyde as substrate, and immunoblot staining for aldose reductase. Chromatofocusing of RPE cells cultured in hypertonic media resulted in a prominent increase in the peak corresponding to aldose reductase compared to the peak height of cells grown in control medium. No increase in aldehyde reductase from RPE cells cultured in hypertonic medium was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aldose reductase in human retinal pigment epithelial cells. 840 90

Endocrine crises can occur in diabetes mellitus, in pituitary failure when there is a lack of ACTH, TSH or ADH secretion, in severe hyper- or hypothyroidism (thyroid storm and myxedema coma), severe hyper- or hypoparathyroidism (parathyroid crisis and tetany), in adrenal failure and in patients with pheochromocytoma or carcinoid tumors. Cushing's syndrome can be associated with psychotic crises. This review describes the most important clinical features and the basic diagnostic and therapeutic aspects of the non diabetic endocrine crises.
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PMID:[Endocrine crises]. 848 76

The increased incidence of thyroiditis reported to occur in diabetes has also been observed in long-term galactose-fed dogs where it is reduced by the administration of aldose reductase inhibitors. Since this suggests that thyroidal changes are linked to the abnormal accumulation of sugar alcohols (polyols), present studies were conducted to confirm the presence of aldose and aldehyde reductases in dog thyroid through isolation and characterization. Aldose and aldehyde reductases were isolated from dog thyroid by a series of chromatographic steps which included gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A and chromatofocusing on Mono P. A third, labile NADPH-reductase was partially purified by gel filtration on Sephadex G-100, affinity chromatography on Matrex Green A and hydroxylapatite chromatography on BIO-GEL HT. The kinetic properties of aldose and aldehyde reductases and their susceptibility to inhibition by aldose reductase inhibitors are similar to those of dog kidney aldose and aldehyde reductases. However, the levels of aldose reductase present in thyroid are extremely low compared to the levels of aldehyde reductase. A third NADPH-dependent reductase, tentatively identified as glyceraldehyde reductase, is also present in dog thyroid. This novel enzyme utilizes NADPH to reduce DL-glyceraldehyde and is clearly distinct from the other aldo-keto reductases in molecular weight, substrate specificity, inhibition by aldose reductase inhibitors and immunological properties. In summary aldose reductase, aldehyde reductase and a third novel glyceraldehyde reductase, all of which can utilize glyceraldehyde as substrate, have been identified and characterized in dog thyroid. Only aldose and aldehyde reductases, which can catalyze the production of polyols and were inhibited by aldose reductase inhibitors, appear to be linked to thyroiditis.
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PMID:NADPH-dependent reductases in dog thyroid: comparison of a third enzyme "glyceraldehyde reductase" to dog thyroid aldehyde reductase. 892 Jun 36

Chlorpropamide (CPM) has been reported to produce impaired water excretion due to the enhancement of renal vasopressin (ADH) action and/or due to centrally enhanced ADH release, but it is still unknown whether CPM gives rise to ADH release with a subsequent hyponatremia in diabetes mellitus (DM), which, in turn, causes an impairment of the central nervous system. In 3 patients with DM, who developed hyponatremia during the treatment with CPM, an acute water load (WL) was carried out in the presence and absence of the drug, and plasma ADH was determined with plasma and urine osmolalities. Moreover, in 2 cases, MRI scans of the brain were taken. In all the patients, acute WL tests failed to suppress completely ADH release in response to changes in plasma osmolality in the presence of CPM, which, in turn, resulted in the impaired water excretion. In the absence of CPM, an acute WL normally suppressed plasma ADH leading to the diuresis. MRI scans illustrated the presence of central pontine myelinolysis. It is likely that CPM might stimulate ADH release in DM with a subsequent hyponatremia and brain damages.
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PMID:Chlorpropamide-induced ADH release, hyponatremia and central pontine myelinolysis in diabetes mellitus. 892 90

Recent reports suggest that excess amounts of sugar alcohol are linked to leukocyte dysfunctions associated with diabetes. As the polyol pathway has not been firmly established in leukocytes, we have investigated NADPH-dependent reductases and sugar alcohol formation in dog leukocytes. NADPH-dependent reductase activity was observed with DL-glyceraldehyde as substrate in both mononuclear and polymorphonuclear leukocytes isolated from dog. By chromatofocusing, this activity corresponded primarily to aldehyde reductase rather than aldose reductase. The enzymatic conversion of glucose to the sugar alcohol sorbitol in leukocytes was confirmed in vitro by 19F nuclear magnetic resonance (NMR) spectroscopy using 3-deoxy-3-fluoro-D-glucose as substrate. The NMR spectrum obtained after incubation with 10 Mm 3-deoxy-3-fluoro-D-glucose at 37 degrees C for 24 h displayed newly formed 3-deoxy-3-fluoro-D-sorbitol and 3-deoxy-3-fluoro-D-fructose peaks with both mononuclear and polymorphonuclear leukocytes. Sugar alcohol production in leukocytes from galactose-fed dogs was also observed in vivo. Galactitol accumulation was consistently observed by gas chromatography to occur in mononuclear cells while only trace amounts of galactitol were observed in polymorphonuclear leukocytes. Activation of NADPH oxidase activity in neutrophils isolated from galactose-fed dogs by zymosan was also significantly reduced compared to that of nongalactosemic control dogs. These results indicate that glucose is converted to fructose through sorbitol in both mononuclear and polymorphonuclear leukocytes despite the observations that these cells primarily contain aldehyde reductase rather than aldose reductase. In vivo, sugar alcohol accumulation in mononuclear cells is greater than in polymorphonuclear leukocytes.
J Diabetes Complications
PMID:Polyol pathway and NADPH-dependent reductases in dog leukocytes. 897 81

Aldo-keto reductases (AKRs) are a family of monomeric oxido-reductases with molecular weight ranging from 35-40 kDa and currently includes upwards of 60 members. They are expressed in a wide variety of tissues, where they catalyze the NADPH-dependent reduction of various aliphatic and aromatic aldehydes and ketones. The functions of most of the family members are not well defined. But two members, aldehyde reductase (AKRIA) and aldose reductase (AKRIB), have been extensively studied. The latter has received the most attention since being relevant to the complications of diabetes mellitus. It is up-regulated during hyperglycemia, and at the same time there is an increased activity of the sorbitol pathway and non-enzymatic glycation of proteins with ensuing damage in various tissues. It is developmentally regulated in the ocular lens, and is believed to modulate lens fiber morphogenesis during fetal life. Unlike the other AKR family members that are ubiquitously expressed, recently a renal-specific oxio-reductase has been described that is expressed exclusively in the proximal tubules. Although, it has no homology with other AKR members, it binds to NADPH with high affinity and is up-regulated in streptozotocin-induced diabetes in mice. It is also developmentally regulated and seems to selectively modulate renal tubulogenesis during embryonic life.
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PMID:Relevance of aldo-keto reductase family members to the pathobiology of diabetic nephropathy and renal development. 1149 47


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