UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

The substrate specificities of human aldose reductase and aldehyde reductase toward trioses, triose phosphates, and related three-carbon aldehydes and ketones were evaluated. Both enzymes are able to catalyze the NADPH-dependent reduction of all of the substrates used. Aldose reductase shows more discrimination among substrates than does aldehyde reductase and is generally the more efficient catalyst. The best substrate for aldose reductase is methylglyoxal (kcat = 142 min-1, kcat/Km = 1.8 x 10(7) M-1 min-1), a toxic 2-oxo-aldehyde that is produced nonenzymatically from triose phosphates and enzymatically from acetone/acetol metabolism. D- and L-glyceraldehyde and D- and L-lactaldehyde are also good substrates for aldose reductase. The aldose reductase-catalyzed reduction of methylglyoxal produces 95% acetol, 5% D-lactaldehyde. Further reduction of acetol produces only L-1,2-propanediol. Acetol and propanediol are two products that accumulate in uncontrolled diabetes. Both acetol and methylglyoxal were compared with glucose for their abilities to produce covalent modification of albumin. All three of these carbonyl compounds reacted with albumin to produce modified proteins with new absorption and emission bands that are spectrally similar. Both methylglyoxal and acetol are much more reactive than glucose. A new integrative model of diabetic complications is proposed that combines the aldose reductase/polyol pathway theory and the nonenzymatic glycation theory except that emphasis is placed both on methylglyoxal/acetol metabolism and on glucose metabolism.
...
PMID:Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications. 153 26

There is a marked difference in insulin secretion between the ob+/ob+ obese mouse and its non-obese littermate. Numerous peptides have been implicated in the modification of postprandial insulin secretion. In this study, the morphological and immunohistochemical studies of the genetically obese mouse (ob+/ob+) pancreata were compared with control littermates. Additionally, the distribution of gastric inhibitory polypeptide, somatostatin, glucagon, and insulin immunoreactive cells was also quantitated. Hyperglycemia and hyperinsulinemia were verified in the obese mice. The control animals had some islets and ductules with mononuclear infiltrations of a possible immune character. The obese individuals had a marked increase in both number and size of the islets of Langerhans compared with lean controls. The insulin immunocytochemical reaction in the obese pancreatic beta-cells was weaker than that of controls, as was the aldehyde-fuchsin reaction. The glucagon, gastric inhibitory polypeptide, and somatostatin containing cells were intermingled with the beta-cells. In contrast, the control animals showed a peripheral localization of these cell types. The morphometric analysis of the obese pancreas showed a decreased proportion of non-beta cells within the islets but not in total pancreatic volume in comparison with controls. The obese mouse also had cavities filled with eosin-stained material among numerous beta-cells. No complete epithelial lining distinguished these formations from the surrounding islet cells. The content of the cavities was not stained by any of the immunocytochemical reactions applied. In conclusion, the pancreatic islets of the ob+/ob+ mouse show marked differences in both morphological and immunocytochemical characteristics if compared with control littermates. These differences in architecture may be related to the eventual development of diabetes mellitus in the ob+/ob+ mouse.
...
PMID:A morphological and immunohistochemical investigation of endocrine pancreata from obese ob+/ob+ mice. 167 42

Previous studies have demonstrated altered acetaldehyde metabolism in diabetics with macroangiopathy. Elimination of acetaldehyde in blood homogenates was studied in 20 non-diabetic survivors of myocardial infarction and 22 healthy controls. The half-life of acetaldehyde was shorter in patients, than in controls (mean values 83 and 150 minutes, respectively, p less than 0.001). Thus, the presence of diabetes is not a prerequisite for altered acetaldehyde metabolism in angiopathy patients. Elimination of acetaldehyde proved to be an enzymatic process, as the elimination was virtually abolished in the presence of chloral hydrate, an inhibitor of aldehyde dehydrogenase. In a previous study, however, results of a more specific assay of aldehyde dehydrogenase showed no correlation to the half-life of acetaldehyde. A possible explanation of the rapid acetaldehyde elimination in angiopathy patients is a low capacity of blood proteins for acetaldehyde binding.
Diabetes Res 1991 Feb
PMID:Altered metabolism of acetaldehyde in blood is not a specific marker of diabetic macroangiopathy. 181 8

It has been previously demonstrated that non-enzymatic glycosylation and subsequent cross-linking of proteins can occur at high or greater than physiological concentrations of glucose. Soluble collagen was incubated in the presence of increasing glucose concentrations. The amount of cross-linked collagen was determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Our findings reveal that cross-linking due to non-enzymatic glycosylation occurs at or near physiological concentrations of glucose (3.11-4.22 mM). In addition, this glucose induced cross-linking is a time dependent reaction. When collagen was incubated with a variety of different carbohydrates it was found that ketoses are more active cross-linking agents than aldoses. The addition of a reactive group (such as an amine) alpha to the aldehyde group on the carbohydrate increases the cross-linking activity of glucose 2.8 fold. Blockage of the reactive group alpha to the aldehyde (such as N-acetyl glucosamine or 2-deoxy-D-glucose) totally abolishes glycosylation activity. Both 5-C and 7-C carbohydrates are more active than 6-C carbohydrates. Thus, although glucose may be the most abundant carbohydrate capable of non-enzymatic glycosylation and subsequent cross-linking, it is not the most chemically reactive. However, the significance of these findings to the pathogenesis of diabetes needs to be defined.
Diabetes Res 1991 Jan
PMID:Effect of carbohydrate structure and concentration on the non-enzymatic glycosylation and subsequent cross-linking of collagen. 181 96

Osteopenia is a recognized complication of diabetes mellitus in humans and experimental animals. We recently found that tetracyclines prevent osteopenia in the streptozotocin-induced diabetic rat and that this effect was associated with a restoration of defective osteoblast morphology (Golub et al., 1990). The present study extends these initial ultrastructural observations by assessing osteoblast function in the untreated and tetracycline-treated diabetic rats. After a 3-week protocol, non-diabetic control and diabetic rats, including those orally administered a tetracycline, minocycline (MC), or a non-antimicrobial tetracycline analog (CMT), were perfusion-fixed with an aldehyde mixture; the humeri were dissected and processed for ultracytochemical localization of alkaline phosphatase (ALPase) and Ca-ATPase activities. Some rats from each experimental group received an intravenous injection of 3H-proline as a radioprecursor of procollagen, and the humeri were processed for light microscopic autoradiography. In addition, the osteoid volume in each experimental group was quantitatively examined by morphometric analysis of electron micrographs. During the diabetic state, active cuboidal osteoblasts in the endosteum of control rats were replaced by flattened bone-lining cells that contained few cytoplasmic organelles for protein synthesis (Golgi-RER system), and active transport (mitochondria). Treating diabetic rats with MC, and even more so with CMT, appeared to "restore" osteoblast structure. During diabetes, bone-lining cells incorporated little 3H-proline or secreted little labeled protein and produced only a very thin osteoid layer. Tetracycline administration to the diabetics increased both the incorporation of 3H-proline by osteoblasts and their secretion of labeled protein toward the osteoid matrix, in a pattern similar to that seen in the non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Tetracycline administration restores osteoblast structure and function during experimental diabetes. 183 18

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension. Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol- or acetaldehyde-altered proteins, and questionably enhanced by viral hepatitis. Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug-induced injuries, jejunoileal bypass, and related "shortcircuiting" of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen is the prime example.
...
PMID:Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. 205 45

Twenty seven subjects with Type II diabetes mellitus underwent analysis of the Self-Administered Alcoholism Screening Test (SAAST) and hemoglobin associated acetaldehyde levels (HbAA). The SAAST scores and HbAA levels correlated with one another (r = .48, p = 0.009). No correlation between glycated hemoglobin levels (GHb) and HbAA levels or SAAST was found. Glucose incubation of whole blood led to an increase in GHb but no change in HbAA. We conclude that HbAA and SAAST correlate with each other when measured in patients with diabetes. Therefore each test appears clinically useful in quantifying alcohol consumption in individuals with Type II diabetes mellitus.
...
PMID:Hemoglobin associated acetaldehyde correlates with the Self-Administered Alcoholism Screening Test but not glycated hemoglobin in type II diabetes mellitus. 206 32

Insulin-deficient, adult, diabetic rats were administrated a tetracycline (either minocycline or a chemically-modified non-antimicrobial tetracycline: CMT) by oral gavage over a 3-week period. Untreated diabetic and non-diabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline, as a radioprecursor of procollagen in bone, dentine and periodontal ligament (PDL) or of amelogenin in enamel; perfusion fixation with an aldehyde mixture was carried out at 20 minutes and 4 hours after isotope injection. The parietal bones (calvaria), mandibules including molars, and lower incisors of these rats were dissected and processed for light microscopic autoradiography to study 3H-proline utilization by osteoblasts, PDL fibroblasts, odontoblasts and ameloblasts. In the control rats, at 20 minutes after 3H-proline injection, silver grains of labeled precursor were detected in the osteoblasts of the periosteal surfaces of the parietal bones. At the 4 hour time period, although some radioprecursor was still present in the osteoblasts, most had progressed to the osteoid matrix. In contrast, the flattened bone-lining cells in the untreated diabetics showed minimal uptake and secretion of labeled proline at both time periods. In both minocycline- and CMT-treated diabetic rats, the labeled proline was localized in the osteoblasts and the osteoid in a pattern reminiscent of that seen in the control rats at both time periods. Of interest, CMT administration appeared to increase the labeling of the osteoid matrix more than minocycline treatment. In non-diabetic control rats, the PDL fibroblasts exhibited a polarized elongated profile and incorporated and secreted radioprecursor similar to that described for the osteoblasts in these animals. The PDL fibroblasts in the untreated diabetics lost their regular arrangement and incorporated little if any 3H-proline; once again, tetracycline administration appeared to normalize, at least in part, the structure and 3H-proline incorporation by these connective tissue cells. In contrast, diabetes and tetracycline administration did not affect the incorporation and secretion of radioprecursor by odontoblasts and secretory ameloblasts during tooth development.
...
PMID:Insulin-deficient diabetes impairs osteoblast and periodontal ligament fibroblast metabolism but does not affect ameloblasts and odontoblasts: response to tetracycline(s) administration. 214 81

Aldehyde reductase [EC 1.1.1.2] and aldose reductase [EC 1.1.1.21] are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds. These enzymes are implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Enzyme inhibition as a direct pharmacokinetic approach to the prevention of diabetic complications resulting from the hyperglycemia of diabetes has not been effective because of nonspecificity of the inhibitors and some appreciable side effects. To understand the structural and evolutionary relationship of these enzymes, we cloned and sequenced cDNAs coding for aldose and aldehyde reductases from human liver and placental cDNA libraries. Human placental aldose reductase (open reading frame of 316 amino acids) has a 65% identity (identical plus conservative substitutions) to human liver and placental aldehyde reductase (open reading frame of 325 amino acids). The two sequences have significant identity to 2,5-diketogluconic acid reductase from corynebacterium, frog rho-crystallin, and bovine lung prostaglandin F synthase (reductase). Southern hybridization analysis of human genomic DNA indicates a multigene system for aldose reductase, suggesting the existence of additional proteins. Thus, the aldo-keto reductase superfamily of proteins may have a more significant and hitherto not fully appreciated role in general cellular metabolism.
...
PMID:The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. 249 33

The combined effects of cyclosporin (CYA) and prednisolone (PSL) on the function and morphology of pancreatic B cells of Wistar rats were investigated. Four 13-day treatment groups were compared; these were the O group (olive oil alone, p.o.), the P group (PSL 3 mg/kg/day, i.m.), the C group (CYA 20 mg/kg/day, p.o.), and the PC group (PSL 3 mg/kg/day, i.m. plus CYA 20 mg/kg/day, p.o.). Glucose tolerance was equally impaired in the C and PC groups. The pancreatic insulin content in the C group was 49.7% of that of the O group, whereas that in the PC group was 81.1%. Morphometric analysis using modified aldehyde-fuchsin staining revealed that 'percent beta-granule area' in the islet was 17.5%, 15.0%, 6.5%, and 7.8% in the O, P, C, and PC groups, respectively. Ultrastructurally, pancreatic B cells in the PC group showed CYA damage; however, a significant number of B cells exhibited hypertrophy of the rough endoplasmic reticulum and the Golgi apparatus, suggesting concomitant B cell hyperactivity in this group. These findings suggest that PSL does not aggravate the toxic effects of CYA on pancreatic B cells during short-term treatment; rather, it might be protective.
Diabetes Res Clin Pract 1989 Apr 01
PMID:The effect of prednisolone on cyclosporin-induced damage of pancreatic B cells in Wistar rats. 265 67

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>