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

The matrix adenine nucleotide pool size of rat liver mitochondria was low at birth (2.6-3.0 nmol ATP + ADP + AMP/mg mitochondrial protein). After parturition, the pool size was increased by 50-75% within 1 h, which was sufficient for full development of state 3 respiration rates. The adenine nucleotide pool size continued to increase to 100-150% of the value at birth by 2-3 h postnatal. The ATP/ADP ratio in isolated mitochondria also increased postnatally, to about double the value at birth by 3 h. There were no matrix volume changes over this postnatal period, so the increased ATP + ADP + AMP pool size and the increased ATP/ADP ratio together inferred an overall increase of about 5-fold in the matrix ATP concentration under aerobic conditions. The postnatal uptake of adenine nucleotides into mitochondria occurred at a slower rate in newborns that were hypoxic (11% 02) and in newborns of diabetic mothers (diabetes induced on day 5 of gestation by streptozotocin injection). The normal increase in matrix ATP content is responsible for the rapid stimulation of pyruvate carboxylation (an ATP-requiring matrix reaction) and this in turn contributes to the rapid postnatal onset of gluconeogenesis. The results suggest that delayed adenine nucleotide uptake into liver mitochondria may retard initiation of gluconeogenesis in newborns experiencing hypoxia, as in respiratory distress or in newborns of diabetic mothers. We speculate that this mechanism contributes to the persistent hypoglycemia that is typical of these at-risk newborns.
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PMID:Neonatal hypoxia or maternal diabetes delays postnatal development of liver mitochondria. 356 26

Fibrinogen-platelet interaction was studied in suspensions of platelets obtained from patients with uncontrolled diabetes mellitus of long duration and from control individuals. Fibrinogen binding sites were exposed by stimulating platelets with ADP or with chymotrypsin. There was no significant difference in fibrinogen mediated aggregation between ADP-stimulated platelets of 80 control and 47 diabetic subjects. The Km values for fibrinogen mediated aggregation of ADP-stimulated platelets obtained from control and diabetic donors were 1.39 +/- 0.13 X 10(-7)M and 1.44 +/- 0.13 X 10(-7)M; the Vmax values (expressed in arbitrary light transmission units) were 87.8 +/- 3.14 and 92.8 +/- 4.5 (mean +/- S.E.M.). The analysis of variance showed no significant relationship between Km, Vmax, age and sex in control group; in patient group there was no significant relationship between Km, Vmax, age, sex, type of diabetes, presence of vascular complications and type of treatment (insulin and/or oral hypoglycemic agents). Fibrinogen mediated aggregation of chymotrypsin-treated platelets showed similar pattern in 25 control and in 25 diabetic donors. In 24 normal individuals and in 24 diabetic patients Scatchard analysis revealed 48,820 +/- 5350 fibrinogen binding sites per one normal platelet (Kd = 4.7 X 10(-7)M) and 45,350 +/- 4663 sites per one diabetic platelet (Kd = 3.5 X 10(-7)M). Our data suggest a normal pattern of interaction between fibrinogen and fully activated platelets of diabetic subjects.
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PMID:Fibrinogen interaction with platelets of diabetic subjects. 360 36

Many patients with diabetes mellitus show increased platelet aggregation and prostaglandin synthesis in response to physiological agents such as ADP and collagen when their platelets are tested in platelet-rich plasma or washed platelet suspensions. However, the relationship between increased platelet aggregation in vitro and increased thrombosis in vivo is difficult to establish with certainty. We have developed an in vivo model system in rabbits which tests the response of platelets in circulating native blood to an arterial vessel wall with limited damage such as might occur in arteries of patients with diabetes mellitus. We have used this model system to investigate whether 5 to 9 weeks of alloxan-induced hyperglycemia increases platelet adhesion and aggregation on a damaged vessel wall in vivo as well as platelet aggregation in vitro. Our results show that rabbit platelet function is not affected by extreme hyperglycemia and suggest that alloxan-induced diabetes in the rabbit may not be a good model for human diabetes mellitus.
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PMID:Alloxan-induced hyperglycemia in rabbits and the response of platelets to aggregating agents in vitro and to exposed subendothelium in vivo. 362 40

Content of ATP and AMP, total intracellular pool of adenine nucleotides, the ratio of adenylate cyclase affecting ratio of ATP/ADP, energy change of the adenylate system as well as potential of adenine nucleotides phosphorylation were decreased in testicular tissue of rats with alloxan diabetes. At the same time, content of ADP and inorganic phosphate was increased as compared with control values. The data obtained suggest that energy metabolism was distinctly impaired in rat testes under conditions of alloxan diabetes, which appears to occur as a result of decrease in AMP biosynthesis and in transformation of the nucleotide into ATP during oxidative phosphorylation. These alterations in the pool of adenylates appear to play an important role in impairments of spermatogenic and endocrine functions of testes in diabetes.
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PMID:[Adenine nucleotide metabolism in the testicular tissue of alloxan diabetic rats]. 363 26

Decrease in V4P, V3 and VP, in coefficient of respiratory control, in the ratio ADP:0 as well as an increase in duration of phosphorylation of ADP involved in oxidation of succinate were found in testes mitochondria from rats with alloxan diabetes (content of glucose 20 +/- 2 mmol/L in blood plasma). If a mixture of malate and glutamate was used as a substrate of oxidation, the rate of mitochondrial respiration and coefficient of respiratory control were decreased in testes of diabetic rats under conditions of all the metabolic states studied. At the same time, sensitivity of NADH-oxidase and succinate oxidase systems to controlled heating (28 degrees) was distinctly decreased in the testes mitochondrial membranes of the impaired animals as compared with controls. The data obtained suggest that distinct functional and, apparently, structure alterations occurred in the testes mitochondrial membranes of rats with alloxan diabetes.
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PMID:[Oxidative phosphorylation, NADH-oxidase and succinate oxidase activity in testicular mitochondria of rats with alloxan diabetes]. 372 76

Conditions were developed to permit the extraction of branched-chain 2-oxoacid dehydrogenase from brain tissue in the state of phosphorylation in which it occurred in vivo. Tissue was cold clamped to prevent interconversion of the enzyme forms without rupturing mitochondrial membranes. Extraction was carried out in the presence of NaF to prevent dephosphorylation of the enzyme complex and in the presence of ADP to prevent phosphorylation. In adult male control rats, approximately 35% of the total enzyme from brain was present in the active form. In brains of diabetic rats, the active fraction was increased to 56%. Total activities did not differ in the two groups of rats.
Diabetes 1986 Sep
PMID:Diabetes increases active fraction of branched-chain 2-oxoacid dehydrogenase in rat brain. 374 6

This study was designed to assess the density characteristics of platelets from controls (N = 10) and three groups of diabetics (N = 32) exhibiting various degrees of glycemic control. With continuous gradients of Percoll, platelets from controls and diabetics (N = 8) with an HbA1 less than or equal to 9% formed a band extending from 1.0625 g/ml to 1.0925 g/ml with a mean platelet density of 1.0775 g/ml. In the two groups of diabetics with HbA1 greater than or equal to 10%, there was an increase in the proportion of low-density platelets recovered on the gradients and the mean platelet density was reduced to 1.0750 g/ml (HbA1 = 10-13%) and 1.070 g/ml (HbA1 greater than or equal to 14%). All three groups of diabetics had normal levels of intraplatelet ATP/ADP and beta-thromboglobulin. It is unlikely that in vivo degranulation of platelets after activation was responsible for the altered density profiles. We propose that abnormal platelet subpopulations with low density but normal intraplatelet granule content were responsible for the changed density profiles.
Diabetes 1986 Oct
PMID:Platelet-density analysis and intraplatelet granule content in young insulin-dependent diabetics. 375 93

The effects of acute and chronic alloxan diabetes on the transmembrane electrical activity of rat heart papillary muscle were investigated. The action potential duration (APD) appeared markedly prolonged in all diabetic papillary muscles, as compared to normal. This prolongation of ADP, with no difference in the resting potential (RP), resulted from both a lengthening of the complex time course plateau and a slower rate of repolarisation. APD0 (at 0 mV) and APD10 (+10 mV from RP) increased, respectively, an average of 50% and 24% in the acute, and 72% and 98% in the chronic diabetics as compared to control, whereas Vmax and overshoot (OS) were unchanged. Varying [Ca]o between 0.5 and 3.5 mM did not induce any change in the RP of either control or diabetic papillary muscles. Conversely, there were differences, within and between groups, in the amplitude of the OS and in Vmax, depending on the [Ca]o concentration. In particular, OS and Vmax of acute diabetics were markedly reduced at 1.5 mM. This reduction was maintained at concentrations of [Ca]o lower than 1.5, attesting to the greater sensitivity of both acutely and chronically diabetic muscles to a decrease in external calcium. Cd, a Ca-channel blocker, reduced in diabetics the duration of both the complex plateau and the repolarisation phase, suggesting that a Ca inward current was maintained throughout these two phases. Direct evidence for elucidating the mechanism(s) of the observed APD change in diabetics will be obtained only by transmembrane current analysis.
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PMID:Electrophysiological analysis of the sensitivity to calcium in ventricular muscle from alloxan diabetic rats. 380 Aug 47

Patients with diabetes mellitus manifest increased in vitro platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12-14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 +/- 15, before treatment, to 107 +/- 6 mg/dl on the final day (P less than 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05). The reduction in platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c greater than 12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P less than 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly in patients with HbA1c greater than 12% (2.8 +/- 1.3 versus 1.2 +/- 0.6 microM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Nov
PMID:Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients. 393 Mar 25

Human aorta, brain, and muscle aldose reductase, partially purified by DEAE-cellulose (DE-52) column chromatography, is activated 2-2.5-fold on incubation with 10 microM each of glucose-6-phosphate, NADPH, and glucose for 20 min at 25 degrees C. The activation of the enzyme was established by following the NADPH oxidation as well as the sorbitol formation using glucose as substrate. The activated form of aldose reductase exhibited monophasic kinetics with glucose and glyceraldehyde, whereas the unactivated or native enzyme exhibited a biphasic kinetics with both the substrates. The activated enzyme was less susceptible to inhibition by aldose reductase inhibitors such as sorbinil, alrestatin, and quercetrin as compared with the unactivated enzyme. Similarly, the native enzyme was strongly inhibited by some of the phosphorylated intermediates of glycolytic pathway, such as 3-phosphoglycerate, 1,3-diphosphoglycerate, 2,3-diphosphoglycerate, and ADP, whereas the activated enzyme was either not inhibited or inhibition was 20-30% only. Partially purified aldose reductase from the normal human lens exhibited properties similar to the native enzyme of other tissues, whereas the enzyme from clear lens obtained from diabetic subjects with severe hyperglycemia expressed properties similar to the in vitro activated enzyme of aorta, brain, and muscle.
Diabetes 1985 Nov
PMID:Activation of aldose reductase from human tissues. 393 Mar 26


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