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

Isoenzymes NAD-and NaDP MDH were detected in the cardiac muscle of rabbits by disc electrophoresis in polyacrylamide gel. Alloxan diabetes proved to be accompanied by a significant reduction in the activity of mitochondrial NADP MDH (in the reaction of malic decarboxylation) and its increase in cytozol. The activity of NAD-MDH (in the reaction of oxyacetate reduction) was also decreased in various isoenzymes in the myocardium (particularly in the mitochondria) in diabetes. Insulin restored the correlation of the activities of the isoenzymes NAD- and NADP-MDH in the cytostructures of the myocardium disturbed in diabetes.
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PMID:[Activity of NAD- and NADP-dependent malate dehydrogenase isoenzymes in the myocardium of rabbits with alloxan diabetes]. 0 94

Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.
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PMID:[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. 2 43

In the presence of glucose (2 mg/ml), leucine (10 mM) noticeably increased islets' NADPH contents as well as the NADPH:NADP ratio; the changes occurred as soon as 1 min after its addition. NADH concentrations were also increased by leucine. The NADPH:NADP ratio as well as insulin release stimulated by glucose plus leucine were markedly decreased by methylene blue. The thiol oxidants diamide and tert-butyl hydroperoxide also inhibited insulin secretion in response to glucose plus leucine. Employing the perfused pancreas technique, the insulin-releasing action of p-chloromercuribenzoate was further enhanced by leucine. The combined effects were inhibited by tert-butyl hydroperoxide, however. Our data suggest that the insulin-releasing action of leucine depends on the islets' NADPH and reduced glutathione (GSH); in addition, leucine may contribute to insulin secretion by increasing the islet NADPH:NADP ratio and the NADH:NAD ratio. From the data, we assume that the observed increase of NADPH may lead via GSH to an increase in the number of such thiol groups in the beta-cell membrane, which are believed to be related to stimulation of insulin release and, thus, to increase the sensitivity of the beta-cell to stimulation by glucose and/or leucine.
Diabetes 1979 Jun
PMID:Effect of leucine on the pyridine nucleotide contents of islets and on the insulin released--interactions in vitro with methylene blue, thiol oxidants, and p-chloromercuribenzoate. 3 18

In view of reports that accessory pathways of glucose oxidation are enhanced in the diabetic state, we have determined the levels of key enzymes of the glucuronate-xylulose cycle in the livers of diabetic mice and rats. Genetically diabetic mice (db/db) were found to have increased levels of two NADP-linked enzymes of this cycle [NADP-xylitol dehydrogenase and NADP-L-hexonate dehydrogenase (aldehyde reductase II)], whereas other NAD- and NADP-linked dehydrogenase activities of the pathway were not changed. On the other hand, the livers of streptozotocin-diabetic mice and rats showed normal levels of all these enzymes. In the course of this study, evidence was obtained for the presence in db/db mouse liver of low molecular weight material inhibitory for glucose 6-phosphate dehydrogenase. The use of these animal models in diabetes research is briefly discussed.
Diabetes 1979 Sep
PMID:Studies on dehydrogenases of the glucuronate-xylulose cycle in the livers of diabetic mice and rats. 3 60

The oxidation of leucine by hemidiaphragms of control and diabetic rats was studied in vitro. Rats were rendered diabetic with streptozotocin. Hemidiaphragms of diabetic rats produced approximately 50% more 14CO2 during incubation with 0.1 mM [1-14C]leucine than did control muscles. This was observed during incubation with or without glucose and in the presence or absence of a full complement of plasma amino acids. The concentration of leucine in the tissue water of hemidiaphragms from diabetic rats was greater than that in the control muscles before incubation. The specific activity of leucine at the end of 60 min incubation was not significantly different in diabetic and control muscles, indicating that the increased 14CO2 production represented stimulation of leucine oxidation. Hemidiaphragms of diabetic rats released more leucine into the medium during incubation than did control muscles. The stimulating effect of diabetes on leucine oxidation in vitro was reversible by insulin therapy prior to sacrifice. The addition of 5 mM pyruvate to a medium containing glucose inhibited 14CO2 production from [14C]leucine in control muscles, but stimulated leucine oxidation by hemidiaphragms of diabetic rats. Leucine oxidation by hemidiaphragms of diabetic rats was markedly stimulated by the addition of an electron acceptor, 0.02 mM methylene blue, suggesting that the NADH/NAD ratio may be rate-limiting for branched chain amino acid oxidation in muscles of diabetic rats, but not in muscles of controls. We suggest that the accelerated oxidation of branched chain amino acids by muscles may play a role in the acceleration of the muscle protein catabolism and gluconeogenesis which develop during insulin deficiency. The restraining effect of the cellular redox potential on branched chain amino acid oxidation may play a role in the eventual deceleration of protein catabolism during a prolonged fast.
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PMID:The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm. 126 11

At 3-4 degrees C, the transport of 3-O-methyl-D-glucose (30 mM) was severely impaired in islets prepared from adult rats injected with streptozotocin during the neonatal period. However, at 37 degrees C, the first and second phase of glucose-stimulated insulin release were decreased to the same relative extent in perifused islets of diabetic, as compared to control, animals. Moreover, the time-related increase in the oxidative response of the islets to 16.7 mM D-glucose was less pronounced in diabetic than control rats. The activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase in islet homogenates of diabetic rats only represented one-fifth of that found in control rats, whereas the activity of the cytosolic NAD-glycerophosphate dehydrogenase was comparable in both types of rats. This coincided with the fact that a rise in D-glucose concentration from 2.8 to 16.7 mM failed to increase significantly L-[2-3H]glycerol conversion to 3HOH in islets from diabetic rats, in contrast to the situation found in control animals. The activity of 2-ketoglutarate dehydrogenase in islet homogenates when expressed per microgram protein was not different in control and diabetic rats. Likewise, the ratio between D-[6-14C]glucose oxidation and D-[3,4-14C]glucose oxidation and the capacity of either a non-metabolized analog of L-leucine or 3-phenylpyruvate to preferentially stimulated D-[6-14C]glucose oxidation relative to D-[5-3H]glucose utilization were both unaffected in islets from diabetic rats. These findings argue against the existence of a primary defect in the Krebs cycle of diabetic rats. It is proposed that, despite an obvious alteration of the hexose transport system in the islet cells of diabetic rats, the preferential impairment of the B-cell secretory response to D-glucose, as distinct from other secretagogues, in this model of non-insulin-dependent diabetes is mainly attributable to the low activity of FAD-linked glycerophosphate dehydrogenase, resulting in a decreased metabolic flow through the glycerol phosphate shuttle and a reduced rate of aerobic glycolysis.
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PMID:Study of hexose transport, glycerol phosphate shuttle and Krebs cycle in islets of adult rats injected with streptozotocin during the neonatal period. 153 53

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).
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PMID:Changes in AMP deaminase activities in the hearts of diabetic rats. 202 37

To increase knowledge about the defense mechanisms of pancreatic beta-cells exposed to acute injury, the patterns of protection exerted by 3-aminobenzamide and nicotinamide against the effects of streptozotocin have been studied in vivo and in vitro. It was found that 3-aminobenzamide, a strong inhibitor of the NAD-consuming nuclear enzyme poly(ADP-ribose) synthetase, is maximally effective against streptozotocin-induced diabetes in the rat when administered 45-60 min after the beta-cytotoxic agent, unlike nicotinamide, which exerts best protection when given very close to streptozotocin. A partial protection is still afforded by 3-aminobenzamide administered as long as 120 minutes after streptozotocin. In isolated islets, each protective agent, if added to the incubation medium 20 or even 40 minutes after the exposure of the islets to streptozotocin, is able to partially prevent the effects of the damaging drug on glucose-stimulated insulin release. However, best protection in vitro is obtained when either 3-aminobenzamide or nicotinamide is added simultaneously with the toxic agent. Our results support the concept that the reversibility of streptozotocin-induced acute damage in beta-cells depends on the preservation of intracellular NAD pools during critical time intervals. This can be achieved by two different partially overwhelming mechanisms: a) early stimulation of NAD biosynthesis (prevailing effect of nicotinamide) and b) strong inhibition of poly ADP-ribosylation activity (main effect of 3-aminobenzamide).
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PMID:Protection by 3-aminobenzamide and nicotinamide against streptozotocin-induced beta-cell toxicity in vivo and in vitro. 214 20

A film test for the rapid detection of plasma/serum 3-hydroxybutyrate (3-OHB) has been developed. The film contains NAD, nitro blue tetrazolium, 3-OHB dehydrogenase, and diaphorase, and the surface is coated with modified biomembrane and can detect 50-1500 microM 3-OHB within 2-3 min. One drop or 50 microliters of plasma/serum or blood is applied to the film, and the violet color is read via reflectance meter after 2 min. Plasma/serum samples greater than 1500 microM 3-OHB can be measured by dilution with saline. In blood with 40% hematocrit, the color developed is 50% less than with plasma/serum, and this was adjusted in the reflectance meter. A good correlation (r = 0.99) was observed between results with automated and film methods and between visual methods and reflectance meter. In insulin-dependent diabetes mellitus, all 3 subjects with positive ketonuria (+ +), 8 of 12 subjects with mild ketonuria (+), and 7 of 25 subjects without ketonuria exhibited elevation of 3-OHB in blood greater than 200 microM. The results indicate that 3-OHB film is valuable not only in the emergency room for the differential diagnosis between ketoacidotic and nonketotic hypersomolar coma but also as a marker for insulin dependency, energy dependency on fatty acid compared with glucose, and metabolic control of diabetes.
Diabetes Care 1990 May
PMID:Development of stable film test for rapid estimation of blood or plasma 3-hydroxybutyrate. 235 Oct 30

Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.
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PMID:High dose nicotinamide fails to prevent diabetes in BB rats. 253 59


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