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

Using [14-C]lysine protocollagen substrate prepared from chick embryo tibiae, lysyl hydroxylase activity was found in the 17 000 times g supernatant and particulate fractions obtained from homogenates of isolated rat renal glomeruli. Specific activities using the latter as an enzyme source were about 20-30% that of the supernatant. [14-C]Hydroxylysine formation was proportional to substrate and enzyme concentration, and to time for up to 120 min of incubation. Omission of alpha-ketoglutarate and ascorbate in the incubational assay markedly depressed activity. Hydroxylation of substrate by supernatant enzyme from streptozotocin diabetic rats was significantly increased over that of normal. In contrast, the activity of supernatant fractions from glomeruli of pancreatectomized, normoglycemic animals did not differ from that of non-operated controls. It is concluded that elevated glomerular lysine hydroxylase activity accompanies the increased glomerular collagen synthesis found in streptozotocin diabetes, and that chronic hyperglycemia may be implicated in these changes.
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PMID:Glomerular protocollagen lysyl-hydroxylase activity in streptozotocin diabetes. 12 80

The effect of diabetes and insulin on the activities of both prolyl hydroxylase (trivial name; proline,2-oxoglutarate dioxygenase, EC 1.14.11.2) and lysyl hydroxylase (trivial name; lysine,2-oxoglutarate dioxygenase, EC 1.14.11.4) in isolated rat renal glomeruli was determined. Three groups of experimental animals were used: age-matched controls, streptozotocin-diabetic, and insulin-treated streptozotocin-diabetic. Using 14C-labeled lysine or proline hydroxylase substrate prepared from chick embryo tibiae, glomerular 17 000 X g supernatant enzyme was incubated in a complete hydroxylating system for 60 and 120 min Lysyl hydroxylase activity was significantly increased in diabetic preparations, but prolyl hydroxylase activity did not differ from control. Administration of insulin to streptozotocin-injected animals completely restored glomerular lysyl hydroxylase to normal levels. The results suggest that the specific elevation of lysyl hydroxylase relates to the biochemical changes contributory to diabetic nephropathy, and that insulin may reverse this process.
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PMID:Effect of diabetes and insulin on rat renal glomerular protocollagen hydroxylase activities. 18 35

1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA.
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PMID:Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A. 19 89

Considering the important role of the phosphocreatine energy shuttle in contractile function of the heart we decided to study the different components of this shuttle in STZ-induced diabetic rat heart with a known diabetic related cardiomyopathy. Diabetes produced a gradual decline in total CK activity, reaching a maximum of 35-40% decrease after 4 weeks of diabetes, in both atria and ventricles. All of the CK isoenzymes including the mitochondrial CK (CKm) were reduced but to a different extent in these two tissues. The percentage reduction in diabetic ventricles was BB greater than MB greater than CKm greater than MM and in atria was CKm greater than BB greater than MB greater than MM. A major difference between atrium and ventricle was the greater loss of CKm in diabetic atria than diabetic ventricle (75% in atria vs 32% in ventricle). The B subunit seemed to be the one that was affected the most followed by CKm isoenzyme and then the M subunit. The bound myofibrillar CK isoenzyme, expressed as units of activity/mg of myofibrillar protein, was not affected by 4 weeks of diabetes. The high energy phosphates were also reduced in diabetic heart with a greater reduction in phosphocreatine (43-45%) and a smaller change in ATP (27%). Mitochondrial oxidative phosphorylation with alpha-ketoglutarate was reduced (55%) in diabetic heart, whereas, there was no difference when succinate was used as substrate. These changes were reversible by 4 weeks of insulin treatment. The loss of CKm, phosphocreatine and the reduction in mitochondrial oxidative phosphorylation, could result in an inefficient phosphocreatine energy shuttle which could contribute to the cardiac functional defects associated with diabetes.
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PMID:Alteration of the phosphocreatine energy shuttle components in diabetic rat heart. 180 23

In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine. A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O. A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration. This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation. The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate. The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+. Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity. We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
Diabetes 1991 Feb
PMID:Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin. 182 72

Energy stores and intermediates of carbohydrate metabolism were investigated in the freeze-clamped cerebral cortex of the fetus and fasted neonate born to a diabetic canine mother. Prior studies in these same pups demonstrated circulating hyperinsulinemia, depressed free fatty acid levels, and attenuated gluconeogenesis. Hepatic and muscle tissue also demonstrated augmented levels of glycogen, triglycerides, and amino acids. In the present investigation, cerebral tissue from these same pups of diabetic mothers also demonstrated enhanced fetal cerebral glucose and glycogen content. After 24 h of neonatal fasting, cerebral glycogen content declined to values lower than in control pups. Cerebral cortical levels of glucose-6-phosphate, fructose-6-phosphate, lactate, citrate, alpha-ketoglutarate, and malate were not altered, while oxaloacetate was higher at 3 and 9 h and fructose-1,6-diphosphate was higher at 9 and 24 h in the IDM pups. Adenine nucleotide levels and the energy charge were equivalent to those in control pups at each time interval. In contrast, cerebral cortical amino acids of the glutamate group were enhanced in the fetus or neonate of the diabetic mother. Cerebral cortical alanine was increased from 3 to 24 h while aspartate and glutamate were augmented in the fetus and fasted IDM newborn pup. Glutamine was increased at 6 and 24 h, while gamma-aminobutyrate was elevated in the fetus. Cerebral ammonia concentration was not altered. The augmented stores of cerebral carbohydrate and amino acid pools in the fetus and neonate after maternal canine diabetes may serve as oxidizable substrates for the brain during periods of attenuated systemic fuel availability.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Feb
PMID:Enhanced cerebral substrate pools in the fetus and neonate of the diabetic canine mother. 285 42

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

Effects of ammonia on glucagon and insulin secretion from the perfused pancreas of cirrhotic rats were investigated to clarify the occurring mechanism of hypersecretion of pancreatic glucagon in liver cirrhotics. The results were as follows: During ammonia loading, insulin secretion was inhibited in a dose-related manner, whereas glucagon secretion was gradually increased at high concentrations of ammonia (2 mM) in control rats; this tendency was augmented in the presence of alpha-ketoglutarate in cirrhotic rats. On cessation of ammonia loading, a transient but definite increase in glucagon and insulin secretion was observed. Basal plasma glucagon and ammonia levels as well as basal glucagon secretion from the perfused pancreas of cirrhotic rats were significantly higher than in control rats. Basal insulin secretion from the perfused pancreas of cirrhotic rats was not different in spite of high levels of plasma insulin. Glucagon secretory response to glucose and arginine from the perfused pancreas of cirrhotic rats was higher than in the control pancreas, whereas insulin secretion was lower. In these cirrhotic rats, an increase in the number of islet cells, particularly A cells, was observed. These data suggested that hypersecretion of pancreatic glucagon which was responsible for hyperglucagonemia in cirrhotic rats might be attributed to high levels of ammonia and alpha-ketoglutarate in blood as well as to the fluctuation of abnormal ammonia concentration in blood and to the hypertrophy of islets, particularly of the A cell group due to hypersecretion.
Diabetes Res Clin Pract 1986 Jun
PMID:Effect of ammonia on glucagon secretion from the perfused pancreas of cirrhotic rats. 352 23

Branched-chain-amino-acid:alpha-ketoglutarate transaminase and branched-chain alpha-ketoacid dehydrogenase have been assayed in brains of control and of streptozotocin-induced diabetic rats. Enzyme activities were measured in five distinct regions of the brain: cerebellum, pons + medulla, midbrain, thalamus + hypothalamus, and telencephalon. Subcellular distribution of these enzymes in whole brain was assessed by fractionating brain homogenate into cytoplasm, free mitochondria, and synaptosomes. The following enzymes were used as markers: lactate dehydrogenase for cytoplasm, glutamate dehydrogenase for mitochondria, and glutamate decarboxylase for synaptosomes. The activity of the branched-chain amino acid transaminase in all brain regions was considerably higher than that of the branched-chain alpha-ketoacid dehydrogenase. While the highest activity of the transaminase occurred in brain-stem regions, the highest activity of the dehydrogenase was present in cerebellum and telencephalon. Diabetes did not affect the activity of the transaminase, but it caused a decrease in the total activity of the dehydrogenase in midbrain and in thalamus + hypothalamus. The transaminase was localized in the cytoplasmic fraction of whole brain, while the dehydrogenase was enriched in the free mitochondria.
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PMID:Regional and subcellular distribution of enzymes of branched-chain amino acid metabolism in brains of normal and diabetic rats. 407 48

The total activity of pyruvate dehydrogenase (PDH) complex in rat hind-limb muscle mitochondria was 76.4 units/g of mitochondrial protein. The proportion of complex in the active form was 34% (as isolated), 8-14% (incubation with respiratory substrates) and greater than 98% (incubation without respiratory substrates). Complex was also inactivated by ATP in the presence of oligomycin B and carbonyl cyanide m-chlorophenylhydrazone. Ca2+ (which activates PDH phosphatase) and pyruvate or dichloroacetate (which inhibit PDH kinase) each increased the concentration of active PDH complex in a concentration-dependent manner in mitochondria oxidizing 2-oxoglutarate/L-malate. Values giving half-maximal activation were 10 nM-Ca2+, 3 mM-pyruvate and 16 microM-dichloroacetate. Activation by Ca2+ was inhibited by Na+ and Mg2+. Mitochondria incubated with [32P]Pi/2-oxoglutarate/L-malate incorporated 32P into three phosphorylation sites in the alpha-chain of PDH; relative rates of phosphorylation were sites 1 greater than 2 greater than 3, and of dephosphorylation, sites 2 greater than 1 greater than 3. Starvation ( 48h ) or induction of alloxan-diabetes had no effect on the total activity of PDH complex in skeletal-muscle mitochondria, but each decreased the concentration of active complex in mitochondria oxidizing 2-oxoglutarate/L-malate and increased the concentrations of Ca2+, pyruvate or dichloracetate required for half-maximal reactivation. In extracts of mitochondria the activity of PDH kinase was increased 2-3-fold by 48 h starvation or alloxan-diabetes, but the activity of PDH phosphatase was unchanged.
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PMID:Reversible phosphorylation of pyruvate dehydrogenase in rat skeletal-muscle mitochondria. Effects of starvation and diabetes. 633 93


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