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

Nicotinamide adenine dinucleotide (NAD) and its derivatives NADH, NADP and NADPH have regulatory functions in the generation of triose phosphates and pyruvate from glucose. In many studies of the influence of the diabetic state on relationships between pyridine nucleotide and glucose metabolism, the focus has been on the sorbitol pathway. Less attention has been paid to other aspects of the role of pyridine nucleotides in pyruvate formation from glucose, in particular the effects of the NAD precursors nicotinamide and nicotinic acid on glucose metabolism. This paper reviews current knowledge of the involvement of pyridine nucleotides and their precursors in glucose catabolism in the normal and diabetic state. Reference is also made to the following three current hypotheses for mechanisms underlying diabetic microangiopathy: 1. Chronic glucose overutilization, caused by hyperglycemia, in tissues which lack insulin receptors and therefore are freely permeable to glucose. 2. Enhancement of sorbitol pathway activity with an ensuing decrease in the ratio of NAD/NADH. 3. Enhanced utilization of both glucose and pyridine nucleotides in formation of triose phosphates and pyruvate. Therapy with NAD precursors like nicotinamide might have corrective effects on these proposed biochemical aberrations, thereby retarding progression of microangiopathy.
Diabetes Metab Res Rev
PMID:Pyridine nucleotides in glucose metabolism and diabetes: a review. 1070 37

Stress hyperglycemia is common and likely to be associated with at least some of the same complications as hyperglycemia in true diabetes mellitus, such as poor wound healing and a higher infection rate. The predominant cause is the intense counterregulatory hormone and cytokine responses of critical illness, often compounded by excessive dextrose administration, usually as TPN. Although randomized data suggesting benefit of controlling hyperglycemia in hospitalized patients are paltry, prospective controlled trials are feasible and should be initiated. In the interim, the practice at the authors' institution is to use insulin to lower plasma glucose concentrations to a safe range of 150 mg/dL to 200 mg/dL in all patients.
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PMID:Stress-induced hyperglycemia. 1121 23

Streptozotocin-induced diabetic wistar rats were maintained for 4 weeks on a supplement of extracts of yam (Dioscorea cayenensis) or dasheen (Colocassia esculenta). The activities of malic enzyme, NADP+ isocitrate dehydrogenase, Glucose 6-P-dehydrogenase and the transaminases were determined to assess any degree of metabolic alteration caused by diabetic nephropathy. Diabetic rats fed normal diet and those fed yam extract, dasheen extract and commercial linamarin respectively lost weight significantly compared to healthy controls. The diabetic rats fed dasheen extract, maintained near normoglycaemic values compared to diabetic rats on normal diet (P < 0.05). Malic enzyme activity was significantly reduced (P < 0.05) in diabetic rats on the normal diet compared to normal healthy controls. Feeding of yam or dasheen extract raised the activity of this enzyme towards normal. Feeding of dasheen extract or commercial linamarin significantly lowered (P < 0.05) the activity of NADP+ isocitrate dehydrogenase below that of healthy controls. Glucose 6-P-dehydrogenase activity was significantly increased (P < 0.05) in diabetic rats compared to healthy controls. Alanine transaminase in the kidney of diabetic rats fed yam extract was significantly higher than healthy controls (P < 0.05). These results demonstrate an overall aggravation of the diabetic nephropathy by yam and dasheen extracts in the diet. In the Caribbean region where these foods are dietary staples, there may be a correlation with the reported high prevalence of diabetes mellitus and the development of renal disease.
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PMID:Effect of yam (Dioscorea cayenensis) and dasheen (Colocassia esculenta) extracts on the kidney of streptozotocin-induced diabetic rats. 1151 35

Trigonella foenum graecum (fenugreek) seed powder has been suggested to have potential antidiabetic effects. The effect of oral administration of Trigonella whole seed powder (5% in the diet) for 21 days on glycolytic, gluconeogenic and NADP-linked lipogenic enzymes were studied in liver and kidney tissues of alloxan-induced diabetic Wistar rats. Diabetic rats were characterised by a 4-fold higher blood glucose level and a 0.7-fold lower body weight compared to normal controls. The activities of the glycolytic enzymes were significantly lower in the diabetic liver and higher in the diabetic kidney. The activities of gluconeogenic enzymes were higher in both liver and kidney during diabetes, however the activities of the lipogenic enzymes were decreased in both tissues during diabetes. Trigonella seed powder treatment to diabetic rats for 21 days brought down the elevated fasting blood glucose levels to control levels. The altered enzyme activities were significantly restored to control values in both the liver and kidney after Trigonella seed powder treatment. The therapeutic role of Trigonella seed powder in type-1 diabetes as exemplified in this study can be attributed to the change of glucose and lipid metabolising enzyme activities to normal values, thus stabilizing glucose homeostasis in the liver and kidney. These biochemical effects exerted by Trigonella seeds make it a possible new therapeutic in type-1 diabetes.
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PMID:Trigonellafoenum graecum (fenugreek) seed powder improves glucose homeostasis in alloxan diabetic rat tissues by reversing the altered glycolytic, gluconeogenic and lipogenic enzymes. 1169 99

In the traditional system of medicine, Ayurveda, several spices and herbs are thought to possess medicinal properties. Among the spices, turmeric rhizomes (Curcuma longa. Linn.) are used as flavoring and coloring agents in the Indian diet everyday. In this research, we studied the effect of turmeric and its active principle, curcumin, on diabetes mellitus in a rat model. Alloxan was used to induce diabetes. Administration of turmeric or curcumin to diabetic rats reduced the blood sugar, Hb and glycosylated hemoglobin levels significantly. Turmeric and curcumin supplementation also reduced the oxidative stress encountered by the diabetic rats. This was demonstrated by the lower levels of TBARS (thiobarbituric acid reactive substances), which may have been due to the decreased influx of glucose into the polyol pathway leading to an increased NADPH/NADP ratio and elevated activity of the potent antioxdiant enzyme GPx. Moreover, the activity of SDH (sorbitol dehydrogenase), which catalyzes the conversion of sorbitol to fructose, was lowered significantly on treatment with turmeric or curcumin. These results also appeared to reveal that curcumin was more effective in attenuating diabetes mellitus related changes than turmeric.
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PMID:Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. 1185 20

The levels of blood lymphocyte NAD(P)-dependent dehydrogenases were investigated in children and teenagers with different duration of insulin-dependent diabetes mellitus (IDDM). The level of some NAD(P)-dependent dehydrogenases changed proportionally in dependence of IDDM duration and insulin therapy did not restore their activities to the normal level. It is suggested that these changes may reflect decrease of energy metabolism and plastic processes in blood lymphocytes from diabetic children and teenagers reflecting. These changes correspond to altered functional reactivity of immunocompetent cells and represent metabolic basis of immunopathogenic complications of IDDM.
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PMID:[The activity of NAD(P)-dependent dehydrogenases in blood lymphocytes in children and adolescents with different duration of insulin-dependent diabetes mellitus]. 1249 96

The 2-oxoaldehyde methylglyoxal (MeG) is the precursor to a number of the known advanced glycation endproducts (AGE) implicated in the development of diabetic complications. Other 2-oxoaldehydes that are important in AGE formation, such as glyoxal, glucosone, deoxyglucosone, xylosone and deoxyxylosone, are produced by nonenzymatic reactions. By contrast, MeG is produced by both enzymatic and nonenzymatic processes, most of which appear to be enhanced in diabetes. MeG may be a major precursor to formation of AGE, and rates of production of MeG depend upon physiological conditions such as hyperglycemia and ketoacidosis. MeG is also unique compared to the other 2-oxoaldehydes in its complex metabolism. At least four pathways contribute to detoxification of MeG: (1) aldose reductase, a member of the aldo-keto reductase superfamily, catalyzes the NADPH-dependent reduction of a wide range of aldehydes. MeG is the best of the known physiological aldehyde substrates of aldose reductase. The distribution of aldose reductase in human tissue is restricted; there is little expression in liver; (2) the ubiquitous and highly active glyoxalase system converts MeG into D-lactate. However, this system depends upon the availability of glutathione; activity is severely limited by conditions of oxidative stress that impact levels of glutathione; (3) betaine aldehyde dehydrogenase, also known as ALDH9, is able to catalyze the oxidation of MeG to pyruvate, although less efficiently than with its substrate betaine aldehyde; (4) the long-known but not widely studied 2-oxoaldehyde dehydrogenases (2-ODHs) catalyze the oxidation of MeG to pyruvate, primarily in liver. There are two NADP-dependent 2-ODHs in human liver. Both of these require an activating amine. The physiological activator is unknown.
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PMID:Methylglyoxal metabolism and diabetic complications: roles of aldose reductase, glyoxalase-I, betaine aldehyde dehydrogenase and 2-oxoaldehyde dehydrogenase. 1260 21

Diabetes mellitus (DM) is the most common metabolic disease, an independent risk factor of coronary disease, and shortens lifetime in all populations of patients, including kidney transplant recipients. Patients after kidney transplantation are exceptionally predisposed to develop or to exacerbate the preexisting DM. Age, DM in family, CMV infections, genetic factor (HLA A26 and B27), immunosuppressive treatment with steroids or calcineurin inhibitors belong to the major risk factors of diabetes. We analyzed 1300 renal transplant recipients in our center. Out of them 153 suffered from DM. DM de novo revealed 80 pts. Mean age in type I pts was 44.88 years and in type II pts was 57.27 years. De novo diabetics were 56.41 years old in average. CMV infection, potentially pathogenic in development of DM de novo, coexisted in 7.5% of these cases as frequently as in whole TPN population. Most frequently detected HLA antigens were: A2, B8 and DR5. Use of cyclosporine and tacrolimus promoted incidence of DM. We conclude, that low percentage of de novo DM in patients after renal transplantation may result from flexibility in administration of immunosuppressive regimens. Cyclosporine and tacrolimus treatment was switched to sirolimus or mycophenolate mofetil when the glucose intolerance was detected to prevent development of DM.
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PMID:[Treatment of diabetes mellitus in patients after renal transplantation]. 1262 76

Aldo-keto reductases (AKRs) are NAD(P)H-dependent oxidoreductases that catalyse the reduction of a variety of carbonyl compounds, such as carbohydrates, aliphatic and aromatic aldehydes and steroids. We have studied the retinal reductase activity of human aldose reductase (AR), human small-intestine (HSI) AR and pig aldehyde reductase. Human AR and HSI AR were very efficient in the reduction of all- trans -, 9- cis - and 13- cis -retinal ( k (cat)/ K (m)=1100-10300 mM(-1).min(-1)), constituting the first cytosolic NADP(H)-dependent retinal reductases described in humans. Aldehyde reductase showed no activity with these retinal isomers. Glucose was a poor inhibitor ( K (i)=80 mM) of retinal reductase activity of human AR, whereas tolrestat, a classical AKR inhibitor used pharmacologically to treat diabetes, inhibited retinal reduction by human AR and HSI AR. All- trans -retinoic acid failed to inhibit both enzymes. In this paper we present the AKRs as an emergent superfamily of retinal-active enzymes, putatively involved in the regulation of retinoid biological activity through the assimilation of retinoids from beta-carotene and the control of retinal bioavailability.
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PMID:Human aldose reductase and human small intestine aldose reductase are efficient retinal reductases: consequences for retinoid metabolism. 1273 97

Several links relate mitochondrial metabolism and type 2 diabetes or chronic hyperglycaemia. Among them, ATP synthesis by oxidative phosphorylation and cellular energy metabolism (ATP/ADP ratio), redox status and reactive oxygen species (ROS) production, membrane potential and substrate transport across the mitochondrial membrane are involved at various steps of the very complex network of glucose metabolism. Recently, the following findings (1) mitochondrial ROS production is central in the signalling pathway of harmful effects of hyperglycaemia, (2) AMPK activation is a major regulator of both glucose and lipid metabolism connected with cellular energy status, (3) hyperglycaemia by inhibiting glucose-6-phosphate dehydrogenase (G6PDH) by a cAMP mechanism plays a crucial role in NADPH/NADP ratio and thus in the pro-oxidant/anti-oxidant cellular status, have deeply changed our view of diabetes and related complications. It has been reported that metformin has many different cellular effects according to the experimental models and/or conditions. However, recent important findings may explain its unique efficacy in the treatment of hyperglycaemia- or insulin-resistance related complications. Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism (s), which is (are) not completely elucidated as yet. Although it is clear that metformin has non-mitochondrial effects, since it affects erythrocyte metabolism, the mitochondrial effects of metformin are probably crucial in explaining the various properties of this drug.
Diabetes Metab 2003 Sep
PMID:Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. 1450 5


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