Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases.
Diabetes Res Clin Pract
PMID:Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro. 288 8

Protein synthesis and degradation, and redox state were measured in soleus and extensor digitorum longus muscles of rats up to 12 days after injection of streptozotocin. Muscle growth was slower in these animals apparently due to slower protein synthesis throughout the duration of diabetes. Up to day 4 after injection of streptozotocin or withdrawal of insulin from treated, diabetic animals, the muscle ratio of lactate/pyruvate, an indicator of the cytoplasmic NAD+ redox couple, was lower and protein degradation was faster than in control muscles. Thereafter, the ratio of lactate/pyruvate was greater and protein degradation was slower than in size- or age-matched control muscles. Insulin treatment in vitro or in vivo increased lactate/pyruvate and decreased proteolysis. Therefore, in muscles of streptozotocin-diabetic rats, the initial increase and later fall in proteolysis, and the inhibition of proteolysis by insulin, may correlate with opposite changes in NADH/NAD+.
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PMID:Rat muscle protein turnover and redox state in progressive diabetes. 294 34

This study examines the effect of an aldose reductase inhibitor (sorbinil) on the flux of specifically labeled glucose through alternative pathways of metabolism in the lens of normal and diabetic rats 1 wk after the induction of diabetes with alloxan. In the diabetic rat lens, there was an apparent increase in the flux of glucose through the pentose phosphate pathway (PPP), as measured by the difference in the yields of 14CO2 from [1-14C]glucose and [6-14C]glucose [C1-C6], this value was 0.087 +/- 0.005 and 0.263 +/- 0.034 mumol X g lens-1 X h (mean + SE of 6 values) for control and diabetic rats, respectively; sorbinil treatment decreased the values to 0.065 +/- 0.008 and 0.171 +/- 0.028, respectively. With glucose tritiated on carbon 2 or 3, it has been shown that the flux of glucose through the polyol route is increased, whereas the flux through the glycolytic pathway is decreased in the diabetic rat lens; both are restored toward normal in the sorbinil-treated diabetic group. These results suggest that the dual effects of diabetes in increasing the lens content of glucose and glucose 6-phosphate and the flux of glucose in the polyol pathway will result in an increased utilization of NADPH and production of NADH, factors favoring the flow of glucose through the PPP and restricting the glycolytic route in the diabetic rat lens. The inhibition of aldose reductase by sorbinil tends to normalize the redox state of the nicotinamide nucleotides, reimposing the NADPH limitation on the PPP and increasing the availability of NAD+ for the glycolytic route.
Diabetes 1986 Nov
PMID:Effect of aldose reductase inhibitor (sorbinil) on integration of polyol pathway, pentose phosphate pathway, and glycolytic route in diabetic rat lens. 309 2

Increase in content of glucose in aorta as well as in reducing properties of NAD and NADP coenzymes and alteration in content of cofactor of the sorbitol pathway led to accumulation of sorbitol in streptozotocin-diabetic rats. Administration of nicotinamide into diabetic animals induced an increase in the ratios of NAD+/NADH and NADP+/NADPH, accompanied by a decrease in sorbitol formation occurring in the reaction catalyzed by aldose reductase and stimulation of the sugar oxidation in the reaction catalyzed by sorbitol dehydrogenase. Possible use of nicotinamide for prevention and treatment of vascular lesions in diabetes is discussed.
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PMID:[Nicotinamide coenzyme regulation of the sorbitol pathway of glucose metabolism in the aorta of rats with streptozotocin diabetes]. 315 51

The structural peculiarities of rabbit muscle aldolase accompanying enhancement of the aldolase activity in diabetes are described from the data of tryptophan phosphorescence at the room temperature and fluorescence polarization. It is shown that the pathology-concomitant conformational changes occur in both the hydrophobic part and NAD-binding site of the enzyme. The character of the structural changes in the hydrophobic part of the protein in diabetes and an increase in the enzymic activity are similar to that observed in normal aldolase after its interaction with NADH and are believed to be associated with the enhancement of the rigidity in the Trp-147 environment.
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PMID:[Structuro-functional characteristics of aldolase from rabbit muscles in diabetes]. 318 55

Placental estrogen hydroxylase (EH) enzyme activity was measured at term using the catechol-O-methyl transferase coupled method in normal and high risk conditions. The identity and ratio of products formed during incubation of microsomes as analysed by high performance liquid chromatography in chronic hypertension, toxemia and diabetes mellitus was not different from controls. The mean enzymatic activity was also not different among the conditions studied as expressed mean +/- SE pmol/min/mg, protein: chronic hypertension (7.8 +/- 1), toxemia (8 +/- 1.6), diabetes mellitus (6.1 +/- 0.9) and controls (8.3 +/- 1.5). The cofactor dependence of EH was studied showing that NADPH is a better substrate for the enzyme than NADH.
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PMID:Estrogen hydroxylase activity in the human placenta at term. 340 95

A cytochrome has been detected in secretory granules prepared from anglerfish islets of Langerhans. The heme moiety was determined to be of the b type, and the dithionite-reduced cytochrome exhibited an alpha-band maximum at 561 nm with an extinction coefficient of 13.8 mM-1 X cm-1. The protein was present at a concentration of 40 +/- 4 pmol/mg of secretory granule protein. The cytochrome was found to be an integral membrane protein and to be reduced by ascorbic acid but not by NADH, NADPH, reduced glutathione (GSH), or succinate. Because of the similarity to previously characterized secretory granule cytochrome b561's from neuroendocrine tissues, this cytochrome is also referred to as cytochrome b561. Although its function has not yet been elucidated, the apparent specificity for ascorbate suggests that it may be a component of the ascorbate-dependent peptidyl-glycine alpha-amidating monooxygenase system that functions in the amidation of islet hormones.
Diabetes 1986 Aug
PMID:Islet secretory granules contain cytochrome b561. 352 85

D-Glucose increased the cytosolic NADH/NAD+ ratio (but not the cytosolic NADPH/NADP+ ratio), augmented O2 uptake, raised the ATP/ADP ratio, decreased 86Rb outflow, and stimulated insulin release in tumoral insulin-producing cells of the RINm5F line. L-Leucine and 4-methyl-2-oxopentanoate also stimulated insulin secretion. In the RINm5F cells, as in normal islet cells, the nonmetabolized analogue of L-leucine, 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), activated glutamate dehydrogenase, augmented L-[U-14C]glutamine oxidation, and induced a more reduced state of cytosolic redox couples. However, in sharp contrast to either its effect in normal islet cells or that of D-glucose in the tumoral cells, BCH severely decreased O2 uptake, lowered the ATP/ADP ratio, increased 86Rb outflow, and inhibited insulin release in the RINm5F cells. These findings are interpreted to support the concept that the rate of ATP generation represents an essential determinant of the secretory response of insulin-producing cells to nutrient secretagogues.
Diabetes 1987 Feb
PMID:Opposite effects of D-glucose and a nonmetabolized analogue of L-leucine on respiration and secretion in insulin-producing tumoral cells (RINm5F). 354 45

Heart mitochondria from chronically diabetic rats ('diabetic mitochondria'), in metabolic State 3, oxidized 3-hydroxybutyrate and acetoacetate at a relatively slow rate, as compared with mitochondria from normal rats ('normal mitochondria'). No significant differences were observed, however, with pyruvate or L-glutamate plus L-malate as substrates. Diabetic mitochondria also showed decreased 3-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-oxoacid CoA-transferase activities, but cytochrome content and NADH-dehydrogenase, succinate dehydrogenase, cytochrome oxidase and acetoacetyl-CoA thiolase activities proved normal. The decrease of 3-hydroxybutyrate dehydrogenase activity was observed in diabetic mitochondria subjected to different disruption procedures, namely freeze-thawing, sonication or hypoosmotic treatment, between pH 7.5 and 8.5, at temperatures in the range 6-36 degrees C, and in the presence of L-cysteine. Determination of the kinetic parameters of the enzyme reaction in diabetic mitochondria revealed diminution of maximal velocity (Vmax) as its outstanding feature. The decrease in 3-hydroxybutyrate dehydrogenase in diabetic mitochondria was a slow-developing effect, which reached full expression 2-3 months after the onset of diabetes; 1 week after onset, no significant difference between enzyme activity in diabetic and normal mitochondria could be established. Insulin administration to chronically diabetic rats for 2 weeks resulted in limited recovery of enzyme activity. G.l.c. analysis of fatty acid composition and measurement of diphenylhexatriene fluorescence anisotropy failed to reveal significant differences between diabetic and normal mitochondria. The Arrhenius-plot characteristics for 3-hydroxybutyrate dehydrogenase in membranes of diabetic and normal mitochondria were similar. It is assumed that the variation of the assayed enzymes in diabetic mitochondria results from a slow adaptation to the metabolic conditions resulting from diabetes, rather than to insulin deficiency itself.
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PMID:Decreased rate of ketone-body oxidation and decreased activity of D-3-hydroxybutyrate dehydrogenase and succinyl-CoA:3-oxo-acid CoA-transferase in heart mitochondria of diabetic rats. 354 9

It has been established that the pyrogallol autoxidation method for the estimation of the activity of superoxide dismutase (SOD) (EC 1.15.1.1) is superior in precision and sensitivity to a superoxide-generating method (NADH/phenazine methosulfate linked to nitroblue tetrazolium reduction). Reference intervals were established in an urban population in the Far East for SOD activity in erythrocytes using the pyrogallol method, and for glutathione peroxidase (GSH-Px) (EC 1.11.1.9) activity in erythrocytes using a standard glutathione reductase-linked method. On this basis, erythrocyte SOD activities were significantly (P less than 0.05) depressed in cases of visceral cancer, acute myocardial infarct, congestive heart failure, respiratory failure, chronic renal failure, and diabetes mellitus, but within the reference interval in cases of lung cancer and asthma. Erythrocyte GSH-Px activity was significantly (P less than 0.05) depressed in cases of diabetes mellitus and chronic renal failure but elevated in respiratory failure and asthma. GSH-Px and SOD activities were well correlated in patients but not in the reference population.
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PMID:Superoxide dismutase and glutathione peroxidase activities in erythrocytes as indices of oxygen loading in disease: a survey of one hundred cases. 366


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