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

The effects of unilateral nephrectomy (UN) and streptozotocin (STZ) diabetes on the activities of enzymes involved in uridine and cytidine synthesis in early renal growth (3-14 days after stimulus to growth) have been compared. Measurements were also made of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) and of glucose 6-phosphate (G6P), UDP-glucose, and glycogen, in relation to phosphoribosyl pyrophosphate, ribonucleotide, and complex carbohydrate formation. There were striking differences in the activities of CTP synthetase, G6PDH, and 6PGDH in the two conditions, with a three-fold increase in all three enzymes at 3 and 5 days and a two-fold increase above basal values at 14 days of STZ diabetes. The UN group showed no significant change in CTP synthetase at any stage and the activity of G6PDH and 6PGDH only kept pace with renal growth. Changes in routes of uridine synthesis were less marked, with a more rapid rise in carbamoyl-phosphate synthetase (glutamine) and a lesser response of dihydroorotate dehydrogenase in the UN relative to the STZ-diabetic groups. The enzymes of complex II and of uracil phosphoribosyltransferase showed essentially similar patterns during renal hypertrophy in UN and STZ diabetes. The parallel increase in CTP synthetase, G6PDH, and 6PGDH in the kidney in diabetes, also known to increase in growth situations in hepatomas and in renal tumors, is discussed in relation to hormone signals involved in renal growth. The importance of the concentration of CTP, and thus of CTP synthetase, in the CTP-cytidyltransferase reaction, an enzyme with a high Km for CTP, makes the present observation of the striking increase in CTP synthetase in STZ diabetes of particular interest in relation to phosphatidylcholine formation and hormone signal transduction.
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PMID:Uridine and cytidine nucleotide synthesis in renal hypertrophy: biochemical differences in response to the growth stimulus of diabetes and unilateral nephrectomy. 138 Dec

We wished to examine the effects of diabetes on muscle glutamine kinetics. Accordingly, female Wistar rats (200 g) were made diabetic by a single injection of streptozotocin (85 mg/kg) and studied 4 days later; control rats received saline. In diabetic rats, glutamine concentration of gastrocnemius muscle was 33% less than in control rats: 2.60 +/- 0.06 mumol/g vs. 3.84 +/- 0.13 mumol/g (P < 0.001). In gastrocnemius muscle, glutamine synthetase activity (Vmax) was unaltered by diabetes (approx. 235 nmol/min per g) but glutaminase Vmax increased from 146 +/- 29 to 401 +/- 94 nmol/min per g; substrate Km values of neither enzyme were affected by diabetes. Net glutamine efflux (A-V concentration difference x blood flow) from hindlimbs of diabetic rats in vivo was greater than control values (-30.0 +/- 3.2 vs. -1.9 +/- 2.6 nmol/min per g (P < 0.001)) and hindlimb NH3 uptake was concomitantly greater (about 27 nmol/min per g). The glutamine transport capacity (Vmax) of the Na-dependent System Nm in perfused hindlimb muscle was 29% lower in diabetic rats than in controls (820 +/- 50 vs. 1160 +/- 80 nmol/min per g (P < 0.01)), but transporter Km was the same in both groups (9.2 +/- 0.5 mM). The difference between inward and net glutamine fluxes indicated that glutamine efflux in perfused hindlimbs was stimulated in diabetes at physiological perfusate glutamine (0.5 mM); ammonia (1 mM in perfusate) had little effect on net glutamine flux in control and diabetic muscles. Intramuscular Na+ was 26% greater in diabetic (13.2 mumol/g) than control muscle, but muscle K+ (100 mumol/g) was similar. The accelerated rate of glutamine release from skeletal muscle and the lower muscle free glutamine concentration observed in diabetes may result from a combination of: (i), a diminished Na+ electrochemical gradient (i.e., the net driving force for glutamine accrual in muscle falls); (ii), a faster turnover of glutamine in muscle and (iii), an increased Vmax/Km for sarcolemmal glutamine efflux.
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PMID:A role for membrane transport in modulation of intramuscular free glutamine turnover in streptozotocin diabetic rats. 146 65

Measurements have been made of the activities of the enzymes of the de novo and salvage pathways of pyrimidine synthesis (carbamoyl phosphate synthetase II (glutamine) (EC 6.3.5.5); dihydroorotate dehydrogenase (EC 1.3.99.11); the overall activity of Complex II (orotate phosphoribosyl pyrophosphate transferase (EC 2.4.2.10) and orotidine 5-phosphate decarboxylase (EC 4.1.1.23); uracil phosphoribosyltransferase (EC 2.4.2.9)) in the mammary gland of rats at different stages of the lactation cycle and the effects of diabetes on the activity of these enzymes in lactation have been studied. From a consideration of the changes in enzyme activities and the changes in the tissue concentration of phosphoribosyl pyrophosphate, an activator of the de novo pathway and substrate for both the de novo and salvage routes, it is concluded that the de novo pathway is the major route of pyrimidine synthesis in mammary tissue. Diabetes decreases the activity of the enzymes of the de novo pathway; the effects are particularly marked for Complex II. The present results on pyrimidine synthesis are compared to the pattern for purine synthesis previously published.
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PMID:Pyrimidine nucleotide synthesis in the rat mammary gland: changes in the lactation cycle and effects of diabetes. 147 92

We measured net uptake and release of amino acids in the brain of 7 nondiabetic and six diabetic subjects. Duration of insulin-dependent diabetes (IDDM) was 19.4 +/- 2.1 years. Arteriojugular vein measurements were performed before and after 120 minutes of insulin infusion and ensuing Biostator-regulated normoglycemia. Cerebral blood flow was measured during normoglycemia by 11-CH3-F and positron emission tomography. During hyperglycemia in the IDDM subjects, arterial concentrations of valine and leucine were higher, and those of glutamic acid and arginine lower, than in nondiabetic subjects. Insulin infusion lowered levels of most amino acids in both groups. Insulin treatment did not significantly affect the uptake or release of amino acids. Significant net uptake of branched-chain amino acids was noted in both groups, as well as uptake of lysine and phenylalanine in the IDDM subjects. The sum of measured differences was not different from zero in either group. Nitrogen balance depended on impressive release of glutamine from the brain (-963 +/- 147 and -960 +/- 303 nmol/100 g/min), which amounted to 73% and 69% of net release in nondiabetic and IDDM subjects, respectively. We conclude that balance between uptake and release of amino acids is similar in nondiabetic and in long-term IDDM subjects.
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PMID:Brain uptake and release of amino acids in nondiabetic and insulin-dependent diabetic subjects: important role of glutamine release for nitrogen balance. 153 41

Periportal hepatocytes around the afferent vessels and perivenous hepatocytes around the efferent vessels of the liver acinus exhibit different metabolic capacities and subcellular structures. This observation led to the concept of the metabolic zonation of the liver acinus. Oxidative energy metabolism, gluconeogenesis, urea synthesis, bile formation and protective metabolism are catalyzed mainly in the periportal zone; glycolysis linked to liponeogenesis, glutamine synthesis and xenobiotic metabolism are predominant in the perivenous zone. This zonation is dynamic rather than static. Zonation develops gradually, depending on perinatal changes of the hepatic circulation and on postnatal alterations of the supply with energy substrates. Zonation also is modulated during puberty. Moreover, adaptation to longer-lasting physiological and pathological alterations occurs as observed during starvation and refeeding, diabetes and regeneration after partial hepatectomy or zonal necrosis. Periportal to perivenous gradients of oxygen, hormones and metabolites, as well as zonal differences in the hepatic innervation, seem to be responsible for the heterogeneous gene expression within the liver acinus.
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PMID:Metabolic heterogeneity of hepatocytes across the liver acinus. 154 56

Magnetic resonance spectroscopy (MRS) is a flexible tool with real clinical utility. Examples from our experience in over 250 cases of clinical proton MRS are presented. Shorter echo time and reproducible water suppression increases the number of metabolites which can be detected and identified. Case reports illustrate the significance of altered ratios of N-acetylaspartate, choline, total creatine, myo-inositol, glutamate, glutamine, lactate, glucose, ketones, and, as an incidental finding, ethanol. Significant new information has resulted by applying proton MRS in chronic hepatic encephalopathy, diabetes mellitus and severe hypoxic encephalopathy ('near-drowning'). Potentially useful measurements have been made in normal brain maturation, ethanol related diseases, dementia (normal-pressure hydrocephalus), urea cycle defect and neuronal disease presenting as seizures. Metabolite imaging, particularly with proton, is clinically valuable, documenting the heterogeneity of biochemical disorders in seemingly focal lesions. A new method of specific 31-phosphorus--phosphocreatine imaging provides information in partially denervated skeletal muscle and is expected to have applications in brain.
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PMID:Clinical tools for the 90s: magnetic resonance spectroscopy and metabolite imaging. 156 13

To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.
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PMID:Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats. 167 65

Localized 1H NMR spectra of human brain in vivo are affected by signal overlap, strong spin-spin coupling, and complex J modulation, and therefore differ considerably from those obtained at higher magnetic fields. This paper deals with the assignment of 1H NMR resonances of cerebral metabolites under the experimental conditions used for human investigations. Conventional 7.0-T FID spectra and 2.0 T localized, short echo time STEAM spectra (TE = 20 ms) of aqueous metabolite solutions are compared to in vivo brain spectra of human volunteers and patients. In addition to singlet resonances from N-acetyl aspartate (NAA), creatines, and cholines, short echo time STEAM spectra exhibit multiplets due to the NAA aspartyl group, glutamate, taurine, and myo-inositol. Enhanced levels of cerebral glutamine are detected in patients with liver cirrhosis. For the first time elevated levels of brain glucose are observed in patients with diabetes mellitus.
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PMID:On the identification of cerebral metabolites in localized 1H NMR spectra of human brain in vivo. 167 88

Insulin responses to nutrient secretagogues were investigated in neonatally streptozotocin-injected (n-STZ) rats, i.e. an animal model of noninsulin-dependent diabetes. In the perfused pancreas 16 mM L-glutamine induced and 10 mM octanoate tended to induce (P less than 0.2) higher responses in n-STZ than in nondiabetic rats. Addition of 3.9 mM glucose potentiated responses to glutamine and octanoate more in n-STZ (3.3- and 3.4-fold) than in nondiabetic rats (1.5- and 1.9-fold). Conversely, the succinate derivative succinate monomethylester (Succ ME) induced lesser response in n-STZ rats (57% of that in nondiabetic rats) and coperfusion with 3.9 mM glucose increased the response less in n-STZ (1.4-fold) than in nondiabetic rats (3.8-fold). Pyruvate (20 mM) mimicked the potency of 3.9 mM glucose, i.e. pyruvate potentiated the response to Succ ME only nonsignificantly (1.2-fold) in n-STZ but markedly (4.9-fold) in nondiabetic rats. Dichloroacetate (20 mM) failed to affect the response to Succ ME together with pyruvate in n-STZ rats. To investigate the role of hyperglycemia for octanoate-induced secretion, nondiabetic rats were made hyperglycemic by 48-h glucose infusions. Octanoate-induced secretion from perfused pancreas was enhanced 3.8-fold after moderate hyperglycemia (13.2 +/- 0.6 mM) and 17-fold after marked hyperglycemia (22.7 +/- 0.6 mM). This positive association between response and degree of hyperglycemia was not found with a nonnutrient secretagogue, 3-isobutyl-1-methylxanthine. Results with glutamine and octanoate indicate that oxidation of nonglucose nutrients which normally do not regulate secretion is enhanced secondary to chronic hyperglycemia. Results with Succ ME and pyruvate suggest that early steps of oxidation of glucose are impaired in n-STZ rats.
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PMID:Multiple abnormalities in insulin responses to nonglucose nutrients in neonatally streptozotocin diabetic rats. 170 69

Metabolism of glutamine (Gln, 2 mM) and glucose (5 mM) was studied in vitro in isolated resident peritoneal macrophages from both normal (BBn) and spontaneously diabetic BB (BBd) rats. The major products from Gln were ammonia, glutamate, CO2 and to a lesser extent aspartate. Glucose decreased (P less than 0.01) the production of ammonia, CO2 and aspartate from Gln by 34-60%, but had no effect on the amount of glutamate accumulated. The major products from glucose were lactate and to a much lesser extent pyruvate and CO2. Gln decreased (P less than 0.01) 14CO2 production from [U-14C]glucose by 19-28%, increased (P less than 0.01) pyruvate production by 35-49%, but had no effect on lactate production. The fraction of glucose metabolized via the pentose phosphate pathway (PC) was less than 5%. There were no significant differences in Gln metabolism between BBn and BBd macrophages. The production of lactate and pyruvate and the flux from glucose into the PC were increased (P less than 0.01) by 2.4, 1.8 and 1.5-fold, respectively, in BBd cells. Increased macrophage glucose metabolism was also observed in diabetes-prone BB (BBdp) rats at 75-80 days but not at 50 days of age. In the presence of both Gln and glucose, potential ATP production from glucose was 2- and 4-times that from Gln, respectively, in BBn and BBd cells. Lactate production was the major pathway for glucose-derived ATP generation. These results demonstrate (a) glycolysis and flux from glucose through the pentose phosphate pathway are enhanced with no alteration in glutaminolysis in BBd macrophages; and (b) glucose may be a more important fuel than Gln for macrophages, particularly in BBd rats. The increased glucose metabolism may be associated with functional activation of the macrophages that have been proposed to be involved in beta-cell destruction and the development of diabetes.
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PMID:Glucose and glutamine metabolism in rat macrophages: enhanced glycolysis and unaltered glutaminolysis in spontaneously diabetic BB rats. 176 69


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