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

Aldose reductase (EC 1.1.1.21) is implicated in the pathophysiology of diabetic complications. In this paper we determined the activities of aldose reductase and ATPases of the erythrocytes in 17 patients with Type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). In the aldose reductase assay we used fluorometric method to avoid the disturbance of hemoglobin. With dihydronicotinamide adenine dinucleotide (NADH), we verified it was aldose reductase but not aldehyde reductase II that was activated in the erythrocytes of the patients with NIDDM. The aldose reductase activity of the erythrocytes in the patients was significantly higher (P less than 0.01) than that in the controls. The activity of Na+/K(+)-ATPase of the patients was significantly lower (P less than 0.01) than that of the controls. The activities of Ca(2+)-ATPase and Mg(2+)-ATPase on the erythrocyte membranes of the patients were similar to those of the controls. At the same time we measured the seven nucleotide concentrations in the erythrocytes of the patients. In this experiment we used ultrafiltration method, instead of acid precipitation to make it possible to determine dihydronicotinamide adenine dinucleotide phosphate (NADPH) and NADH. The concentrations of ATP, ADP and AMP were similar to those of the controls. The concentrations of NADPH, NAD+ and NADH in the erythrocytes of the patients were significantly lower (P less than 0.01, 0.05 and 0.05 respectively) than those of controls. The concentration of nicotinamide adenine dinucleotide phosphate (NADP+) in the patients was significantly higher (P less than 0.01) than that of controls.
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PMID:Activities of aldose reductase, ATPases, and nucleotide concentrations of erythrocytes in patients with type 2 (non-insulin-dependent) diabetes mellitus. 166 Dec 22

Sprague-Dawley rats were separated in 4 groups. G1 received streptozotocin (ST). G2 received nicotinamide (NC) followed by ST. G3 was a NC control and G4 was a citrate control. The rats were sacrificed after 28 h and the islets isolated. Histamine and histaminase were determined. In the islets there was an increase in histamine content in G1 and a smaller increase in G2. The first two groups differ significantly and also in relation to the control groups. A decrease in islet histaminase does not seem responsible for the increased histamine, since group 2 (NC + ST) which had no diabetes, had a lower activity than group 1 (ST). It is suggested that histamine liberation by ST may be related to the diabetogenic effect of this drug.
Diabetes Res Clin Pract
PMID:Early increase in histamine concentration in the islets of Langerhans isolated from rats made diabetic with streptozotocin. 170 Nov 17

Aldose reductase is the first enzyme in the polyol pathway and catalyses the NADPH-dependent reduction of D-glucose to D-sorbitol. Under normal physiological conditions aldose reductase participates in osmoregulation, but under hyperglycaemic conditions it contributes to the onset and development of severe complications in diabetes. Here we present the crystal structure of pig lens aldose reductase refined to an R-factor of 0.232 at 2.5-A resolution. It exhibits a single domain folded in an eight-stranded parallel alpha/beta barrel, similar to that in triose phosphate isomerase and a score of other enzymes. Hence, aldose reductase does not possess the expected canonical dinucleotide-binding domain. Crystallographic analysis of the binding of 2'-monophospho-adenosine-5'-diphosphoribose, which competitively inhibits NADPH binding reveals that it binds into a cleft located at the C-terminal end of the strands of the alpha/beta barrel. This represents a new type of binding for nicotinamide adenine dinucleotide coenzymes.
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PMID:Novel NADPH-binding domain revealed by the crystal structure of aldose reductase. 173 86

Nicotinamide, a poly (ADP-ribose) synthetase inhibitor, was administered intravenously to massive pancreatectomized dogs (NA group), whereas saline was administered intravenously to massive pancreatectomized dogs (saline group). Stathmokinetic studies were done to clarify the regenerating activities of B-cells. Nicotinamide significantly increased mitotic indices of B-cells after pancreatectomy (p less than 0.01). On the second day after pancreatectomy, mitotic index of B-cells in the NA group (2.00 +/- 0.20%) was higher than that in the saline group (0.25 +/- 0.10%). Though insulin content of pancreatic tissue decreased 2 d after pancreatectomy in the both groups, recovery of insulin content was significantly more immediate and more sufficient in the NA group. Intravenous glucose tolerance tests showed a significantly greater increase of insulin release on the 31st and 62nd day after pancreatectomy, and better glucose tolerance on the 62nd day in the NA group compared with the saline group. These results are considered to be attributed to the regenerating and protecting effects of nicotinamide on B-cells after pancreatectomy, and suggest a clinical value of nicotinamide also in man, especially for Sandmeyer's diabetes.
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PMID:Effects of poly (ADP-ribose) synthetase inhibitor on B-cells of a canine pancreas after massive pancreatectomy. 182 22

The response of rat quadriceps muscle fibers to chronic streptozotocin (STZ) diabetes was studied. Transverse sections of rectus femoris muscle from diabetic and weight-matched control rats were assayed for myofibrilar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR). A quantitative analysis was carried out by an automatic interactive analysis system focused on the fiber type size and distribution. STZ-induced diabetes caused important effects in this muscle, with changes in the distribution of oxidative enzyme reactions, type I fiber hypertrophy, and type II fiber atrophy, which was greater in type IIB than in type IIA. It is concluded that hypoinsulinism produces morphological alterations in proximal skeletal muscle fibers that are similar to those of neurogenic myopathy. Thus the pathological changes in these mammalian muscle fibers could explain the clinical syndrome seen in diabetic patients called "diabetic symmetrical proximal motor neuropathy," perhaps the least understood of the major neuropathic complications of diabetes.
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PMID:Proximal skeletal muscle alterations in streptozotocin-diabetic rats: a histochemical and morphometric analysis. 182 78

In animal models of Type 1 (insulin-dependent) diabetes mellitus macrophages were shown to be the first immunocytes that infiltrate the pancreatic Langerhans islets in the autoimmune process. We now show direct macrophage cytotoxicity against isolated rat islet cells in an electron microscopical study, which permits investigation of the specificity of this process. Freshly isolated islet cells were co-incubated with syngeneic peritoneal macrophages at a target: effector-cell ratio of 1:2. After various time periods, the cells were directly fixed and embedded; the ratio of live and dead cells was evaluated by electron microscopy. Our results demonstrate that activated but not resident macrophages lyse islet cells in a time-dependent manner. After 15 h of co-incubation lysis of islet cells is complete. No islet cell-macrophage contacts and no differences between the lysis of Beta cells or non-Beta cells were observed during the observation period. Islet cells encapsulated in alginate were also lysed by macrophages as a direct proof for soluble mediator(s) of cytotoxicity. Nicotinamide protected islet cells from lysis in a dose-dependent manner. As a result of this electron microscopic study we conclude that even at very low target: effector ratios, activated macrophages lyse syngeneic islet cells regardless of islet cell type via secretion of humoral mediator(s).
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PMID:Macrophage cytotoxicity towards isolated rat islet cells: neither lysis nor its protection by nicotinamide are beta-cell specific. 182 93

The influence of nicotinamide and oxythiamine on the activity of NADPH-producing dehydrogenases of glucoso-6-phosphate, 6-phosphogluconate, malate, isocitrate, as well as concentration and synthesis rate of fatty acids in fatty tissue were studied in experiments on mice with genetically conditioned non-insulin-dependent diabetes and hyperinsulinemia. It has been established that in these diseases the synthesis of fatty acids and their inclusion into lipids are activated without increasing the above enzymes activity. It is shown that nicotinamide and oxythiamine inhibit inclusion of C from glucose into free fatty acids, antivitamin intensifies lipolysis in the fatty tissue of the diseased animals.
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PMID:[Effects of nicotinamide and oxythiamine on the lipogenic parameters of the adipose tissue of mice with non-insulin-dependent type of experimental diabetes mellitus and hyperinsulinemia]. 183 Jul 11

A controlled trial of oral nicotinamide to prevent the onset of diabetes mellitus in high risk children was conducted in two centres. The selection criteria were age less than 16 years, islet cell antibody greater than or equal to 80 IUs, and first phase insulin release less than 5th percentile. All of eight untreated control subjects have developed diabetes, whereas only 1 of 14 treated children has diabetes to date. This data suggests that nicotinamide has an effect in preventing Type 1 (insulin-dependent) diabetes and that randomized controlled studies are now indicated.
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PMID:Prevention or delay of type 1 (insulin-dependent) diabetes mellitus in children using nicotinamide. 183 Aug 60

The development of IDDM results from the destruction of pancreatic beta cells. Genetic factors, various immune system alterations, and environmental factors have been studied as the possible causes of IDDM. The concordance rate for developing IDDM between monozygotic twins approaches 50%, suggesting that genetic factors are necessary, but nongenetic factors such as various immune system alterations and environmental factors also influence the clinical expression of genetic susceptibility. Environmental factors (e.g., viruses, chemicals, and diet) affecting the induction of diabetes may act as primary injurious agents which damage pancreatic beta cells or as triggering agents of autoimmunity. Certain viruses including EMC-D and Mengo virus 2T can directly infect pancreatic beta cells and replicate in the cells. The replication of viruses in the beta cells results in the destruction of the cells within 3 days, and the infected mice develop a diabeteslike syndrome in 3-4 days without the involvement of autoimmunity. In contrast, rubella virus appears to be somewhat weakly associated with autoimmune IDDM in hamsters. In addition, endogenous retrovirus expressed in pancreatic beta cells is clearly associated with the development of insulitis and diabetes in NOD mice. In man, there appears to be no correlation between the detection of islet cell autoantibodies and anti-Coxsackie B viral antibodies in newly diagnosed IDDM. In contrast, persistent infection of CMV and rubella virus appears to be associated with the presence of autoantibodies in newly diagnosed IDDM patients. It is particularly noteworthy that human CMV can induce islet cell autoantibodies that react specifically with a 38 kDa islet cell protein which may represent islet cell-specific antigens in a proportion of CMV-associated IDDM cases. These observations suggest that the association of diabetes with Coxsackie B viruses might be due to cytolytic infection of the beta cells with no link to autoimmunity, while both rubella virus and CMV are probably associated with autoimmune IDDM. A number of structurally diverse chemicals including alloxan, streptozotocin, chlorozotocin, Vacor, and cyproheptadine are diabetogenic mainly in rodents and sometimes in man. Possible mechanisms for beta cell destruction by these chemicals include (a) generation of oxygen free radicals and alteration of endogenous scavengers of these reactive species; (b) breakage of DNA and a consequent increase in the activity of poly-ADP-ribose synthetase, an enzyme depleting nicotinamide adenine dinucleotide in beta cells; and (c) inhibition of active calcium transport and calmodulin-activated protein kinase activity. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of viruses and environmental factors in the induction of diabetes. 207 86

The possible value of radical scavengers in the prevention of beta cell destruction was studied in two animal models of type I diabetes. Eight compounds were tested alone or in combinations. In the low-dose streptozotocin model treatment started 24 hr after the last injection of the beta cell toxin, in the BB rat daily administration was started at 50 days of age (i.e., 20-70 days before diabetes onset). No effect was seen in the low-dose streptozotocin model for 3-aminobenzamide, N-acetyl-DL-homocysteine thiolactone, ebselen, and butylated hydroxyanisole whereas partial suppression of hyperglycaemia was seen in mice receiving cysteamine. In BB rats diabetes development was delayed and partially suppressed by administration of ebselen plus vitamin E plus MaxEPA (fish lipid concentrate), but not when ebselen was replaced by nicotinamide. We conclude that the disease process is not readily modifiable by treatment with exogenous radical scavengers.
Diabetes Res 1990 Feb
PMID:Effects of radical scavengers on the development of experimental diabetes. 209 72


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