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

Hypoglycemic and hypolipidemic effects of nicotinamide in insulin-dependent and noninsulin-dependent types of diabetes have been investigated. Hypoglycemic effect of nicotinamide in alloxan- and streptozotocin-induced diabetes resulted in activation of NAD+ biosynthesis and corresponding alterations in the redox state of free nicotinamide coenzymes. Increase in the free NAD+/NADH ratio was accompanied by inhibition of key gluconeogenic enzymes and by a decrease in the rate of 2-14C-incorporation into glucose in liver tissue and by inhibition of sorbitol formation in lens tissue. Nicotinamide exhibited hypolipidemic effect in db/db mice with noninsulin-dependent diabetes. The agent inhibited the enzyme of primary steps of lipogenesis, altered the structure of intercellular CoA pool and lowered the rate of lipid biosynthesis in liver tissue, thus normalizing blood lipoprotein compositions.
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PMID:[Nicotinamide coenzymes in the regulation of cellular metabolism in various types of diabetes]. 146 5

These studies were undertaken to examine effects of elevated glucose levels on glycolysis, sorbitol pathway activity, and the cytosolic redox state of NADH/NAD+ in isolated glomeruli. Blood-free glomeruli were isolated from kidneys of male, Sprague-Dawley rats using standard sieving techniques, then incubated for one hour at 37 degrees C, pH 7.4, pO2 approximately 500 torr, in Krebs bicarbonate/Hepes buffer containing 5 or 30 mM glucose. Elevated glucose levels increased glucose 6-phosphate, fructose 6-phosphate, total triose phosphates, lactate, the lactate/pyruvate ratio, sorbitol, and fructose, but did not affect sn-glycerol 3-phosphate, pyruvate, or myo-inositol levels. The more reduced glomerular cytosolic redox state (manifested by the tissue lactate/pyruvate ratio) induced by 30 mM glucose was completely abrogated by aldose reductase inhibitors added to the diet two to seven days prior to glomerular isolation. These observations, coupled with evidence linking glucose- and diabetes-induced glomerular dysfunction to increased sorbitol pathway metabolism, support the hypothesis that metabolic imbalances associated with a more reduced ratio of cytosolic NADH/NAD+ (resulting from increased glucose metabolism via the sorbitol pathway) play an important role in mediating glucose- and diabetes-induced glomerular dysfunction.
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PMID:Diabetes-induced glomerular dysfunction: links to a more reduced cytosolic ratio of NADH/NAD+. 151

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

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

To assess early stage autonomic nerve dysfunction, power spectral analyses were conducted on the consecutive RR records of healthy subjects (N/C, n = 21) and age-matched diabetic patients without neuropathy (DNN, n = 11), with peripheral neuropathy alone (DPN, n = 14), and with autonomic neuropathy (DAN, n = 13) during resting, deep breathing, and tilting. From the analyses, power spectral densities of low frequency (0.05-0.1 Hz) component (LF; msec2) and of high frequency (0.2-0.35 Hz) component (HF; msec2) were calculated as expressing sympathetic activity and parasympathetic activity, respectively. In N/C, LF and HF were 466 +/- 332 and 251 +/- 151, respectively. Deep breathing significantly (p less than 0.05 by paired t-test) increased HF to 403 +/- 305 and tilting increased LF significantly to 593 +/- 375. In diabetics as a group, both LF and HF were significantly smaller than those in N/C. DNN showed significantly smaller HFs than N/C. DPN showed a significantly smaller HF during deep breathing (135 +/- 93) and a significant smaller LF during tilting (122 +/- 119) than N/C. DAN showed a significantly smaller HF during deep breathing (49 +/- 49) and a significantly smaller LF during tilting (54 +/- 52) than DPN. Tilting increased LF significantly (p less than 0.001) in N/C but not in diabetics. Deep breathing increased HF significantly (p less than 0.001) in N/C and DNN. HF in diabetics highly correlated with known duration of diabetes. LF in diabetics did not correlate with known duration of diabetes nor level of hemoglobin A1c.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 Jun
PMID:Assessment of early stage autonomic nerve dysfunction in diabetic subjects--application of power spectral analysis of heart rate variability. 181 14

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

Measurements have been made of the tissue content of phosphoribosyl pyrophosphate (PPRibP) and of a range of metabolic intermediates involved in the energy charge of the cell, the glycolytic and pentose phosphate pathways, and of the activity of the enzymes of the pentose phosphate pathway and of PPRibP synthetase (EC 2.7.6.1) in the livers of normal, diabetic, insulin-treated diabetic and starved rats and in livers of rats previously starved and then re-fed with high-fat or high-carbohydrate diets. Diabetes, starvation and high-fat diet all caused a fall in the hepatic PPRibP content, whereas insulin treatment and high-carbohydrate diet raised the tissue content. A positive correlation was shown between the PPRibP content and ATP, energy charge and the cytosolic [NAD+]/[NADH] quotient. A positive association between the PPRibP content and the flux of glucose through the pentose phosphate pathway and the synthesis of ribose 5-phosphate via the oxidative enzymes of that pathway, including ribose-5-phosphate isomerase (EC 5.3.1.6), was also observed. A negative correlation was found between the ADP, AMP and Pi contents, and no correlation existed between PPRibP content and the enzymes of the non-oxidative branch of the pentose phosphate pathway. There was no correlation between hepatic PPRibP content and the activity of PPRibP synthetase measured in vitro. These results are considered in relation to the control of PPRibP synthetase in the liver in vivo.
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PMID:Hepatic phosphoribosyl pyrophosphate concentration. Regulation by the oxidative pentose phosphate pathway and cellular energy status. 244 9

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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