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)

Histomorphometric examination and histological observation of femoral bone were performed on long-standing neonatal streptozotocin-induced diabetic rats (n2STZ, n5STZ) as a human model of non-insulin-dependent diabetes mellitus. The growth and strength of femurs decreased in the STZ diabetic rats. Histomorphometric parameters such as cortical bone thickness, number of metaphysical trabeculae and percent trabecular volume of metaphysical area all significantly decreased in the STZ diabetic rats. There were no significant differences in parameters between the n2STZ and n5STZ diabetic rats. Histological findings demonstrated no significant change in the number of osteoclasts in femur nor change corresponding to osteomalacia. Bone absorption in the STZ diabetic rats appeared unchanged. The plasma calcium level did not change in the STZ diabetic rats, although their plasma phosphate or A1-p levels increased. Circulating 24, 25 (OH)2D3 was significantly lower in the STZ diabetic rats than the controls. However, 25 (OH) D3 or biologically active 1, 25 (OH)2D3 was not different between the controls and STZ diabetic rats. Osteopenia is thus present in the femurs of long-standing neonatal STZ diabetic rats, due in part to abnormal vitamin D metabolism.
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PMID:Alterations in femoral bone histomorphometry and vitamin D metabolism in neonatal streptozotocin-induced diabetic rat. 133 71

An acquired or inherited deficiency of FAD-linked glycerophosphate dehydrogenase activity in the pancreatic islet B-cell was recently proposed to represent a far-from-uncommon contributing factor in the pathogenesis of non-insulin-dependent diabetes mellitus. In the present study, it was investigated whether the postulated genomic defect coincides with the biosynthesis of an enzymic protein with altered catalytic properties and might concern an isoenzyme distinct from that found in extrapancreatic tissues. The activity of FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, was indeed severely decreased in islets from rats injected with streptozotocin. The intrinsic properties of the enzyme were preserved, however, as judged from the affinity for L-glycerol-3-phosphate, the ratio in reaction velocity using either FAD or iodonitrotetrazolium as electron acceptor and the activation of the enzyme by Ca2+. When the same kinetic parameters were compared in islet, liver and spleen homogenates from normal rats, significant differences were observed, however, between these three tissues, suggesting the possible existence of distinct isoenzymes.
Diabetes Res 1992
PMID:Intrinsic properties of FAD-linked glycerophosphate dehydrogenase in islets from normal and streptozotocin-induced diabetic rats. 134 98

A 60-year-old HIV-negative man with known noninsulin-dependent diabetes mellitus and glucose 6-phosphate-dehydrogenase deficiency anemia suffered from chronic recurrent furunculosis since the age of 30. In recent years, his condition had become increasingly severe and the recurrences increasingly frequent. Different measures including continuous therapy with large doses of systemic antibiotics for a period of 6 months failed to prevent the recurrences. Oral treatment with pentoxifylline 400 mg t.i.d. was prescribed, and 2 months later the patient experienced a dramatic and complete remission of his furunculosis. Six months later he was still totally free of lesions while continuing to take the same medication. Pentoxifylline may provide a new and effective approach to the previously difficult and often disappointing problem of the management of patients with chronic recurrent furunculosis.
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PMID:Intractable chronic furunculosis: prevention of recurrences with pentoxifylline. 136 45

Reducing sugars react with protein amino groups to form a diverse group of protein-bound moieties with fluorescent and cross-linking properties. These compounds, called advanced glycosylation end products (AGEs), have been implicated in the structural and functional alterations of proteins that occur during aging and long-term diabetes. Although several AGEs have been identified on the basis of de novo synthesis and tissue isolation procedures, the measurement of AGE compounds in vivo has remained difficult. As an approach to the study of AGE formation in vivo, we prepared polyclonal antiserum to an AGE epitope(s) which forms in vitro after incubation of glucose with ribonuclease (RNase). This antiserum proved suitable for the detection of AGEs which form in vivo. Both diabetic tissue and serum known to contain elevated levels of AGEs readily competed for antibody binding. Cross-reactivity studies revealed the presence of a common AGE epitope(s) which forms after the incubation of diverse proteins with glucose. Cross-reactive epitopes also formed with glucose 6-phosphate or fructose. These data suggest that tissue AGEs which form in vivo appear to contain a common immunological epitope which cross-reacts with AGEs prepared in vitro, supporting the concept that immunologically similar AGE structures form from the incubation of sugars with different proteins (Horiuchi, S., Araki, N., and Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332). None of the known AGEs, such as 4-furanyl-2-furoyl-1H-imidazole, 1-alkyl-2-formyl-3,4-diglycosylpyrrole, pyrraline, carboxymethyllysine, or pentosidine, were found to compete for binding to anti-AGE antibody. These data further suggest that the dominant AGE epitope which forms from the reaction of glucose with proteins under native conditions is immunologically distinct from the structurally defined AGEs described to date.
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PMID:Immunochemical detection of advanced glycosylation end products in vivo. 137 95

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

The addition to different types of cells of an inositol-phosphate glycan, generated by the phospholipase C-catalyzed hydrolysis of a insulin-sensitive glycosyl-phosphatidylinositol (glycosyl-PI), mimics some of the biological effects of this hormone. Recently, a specific, time-, dose-, and energy-dependent transport system for this inositol-phosphate glycan has been identified in isolated rat hepatocytes. Here, we show that streptozotocin-induced diabetes mellitus reduced (by about 60%) the basal content of the insulin-sensitive glycosyl-PI in isolated rat hepatocytes. Moreover, streptozotocin-induced diabetes blocked the hydrolysis of the glycosyl-PI in response to insulin, diminished inositol phosphate-glycan uptake by the hepatocytes, and abolished the stimulatory effect of this compound on glycogen synthesis. All these metabolic changes caused by streptozotocin administration were reversed by treatment of the animals with insulin. Our results support the hypothesis that insulin resistance in streptozotocin-induced diabetic rats is related to the impairment of glycosyl-PI metabolism.
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PMID:Impairment of glycosyl-phosphatidylinositol-dependent insulin signaling system in isolated rat hepatocytes by streptozotocin-induced diabetes. 139 18

1. Liver mitochondrial outer membranes were pre-exposed to media of low (20 mM phosphate) or high salt concentration (20 mM phosphate + 0.3 M KCl) before assay of carnitine palmitoyltransferase (CPT) at 25 degrees C. 2. With membranes from fed rats, exposure to high salt decreased sensitivity of CPT to malonyl-CoA whereas high salt increased sensitivity of CPT to malonyl-CoA in membranes from 48 hr-fasted rats. These changes were paralleled by alterations in the KD for high affinity binding of [14C]malonyl-CoA to outer membranes. 3. Decreasing the CPT assay temperatures from 25 to 10 degrees C caused qualitatively similar changes to those seen on exposure to high salt. 4. The relative content of sphingomyelin was increased 2-fold and 4-fold in liver mitochondrial outer membranes from fasted and diabetic rats respectively. Fasting had no effect on the content of cholesterol whereas diabetes decreased this by a third.
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PMID:Physiological state and the sensitivity of liver mitochondrial outer membrane carnitine palmitoyltransferase to malonyl-CoA. Correlations with assay temperature, salt concentration and membrane lipid composition. 139 5

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.
Diabetes 1992 Oct
PMID:Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy. 139 7

Renal osteodystrophy presents with a spectrum of histologic abnormalities. A new entity characterized by a marked decrease in bone turnover without osteoid accumulation, that is, adynamic bone disease, has recently emerged. This new form was thought to be primarily related to aluminum accumulation. Since aluminum-containing phosphate binders have been widely replaced by calcium salts, adynamic bone disease would be expected to disappear over time. However, not only is adynamic bone disease observed in the absence of aluminum intoxication, its incidence does not seem to have decreased. We conducted a retrospective study in 1,803 patients on chronic maintenance dialysis who were biopsied during the last 10 years and assessed the incidence of adynamic bone disease over time in an effort to elucidate the factors associated with its occurrence. Adynamic bone disease was first seen in 1984 in the laboratory. Its incidence increased gradually over the years and, in 1991, still affected approximately 20% of the patients. The primary factors associated with the occurrence of adynamic bone disease include: (a) aluminum accumulation which is currently found in 60% of the patients on chronic maintenance dialysis undergoing biopsies, (b) increasing age of the patients on dialysis, (c) diabetes, and, possibly, (d) chronic ambulatory peritoneal dialysis. The clinical relevance of adynamic bone disease deserves further study. At present, this entity is associated with a tendency towards hypercalcemia, aging of bone due to stunted bone remodeling, a condition which might be associated with impaired repair of physiologic microdamages, and accumulation of microfractures leading to mechanical incompetence and ultimately to higher risk of fractures.
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PMID:Risk of adynamic bone disease in dialyzed patients. 140 83

Placental glucose transfer and sequestration were investigated in anesthetized control and streptozotocin-diabetic rats by perfusing the fetal side of one placenta in situ while infusing a mixture of [3H]D-glucose (to measure net transfer after metabolism) and [14C]2-deoxyglucose (to estimate tissue sequestration) into the maternal circulation. No difference was found between transfer ratios (perfusate/simultaneous maternal plasma ratio) of [3H]D-glucose (0.35 +/- 0.06, mean +/- SD) and [14C]2-deoxyglucose (0.36 +/- 0.06) in control rats. Ratios were reduced (P < .001) to the same extent in diabetic rats ([3H]D-glucose, 0.13 +/- 0.06; [14C]2-deoxyglucose, 0.15 +/- 0.07). Placental glucose utilization, estimated by the quantity of [14C]2-deoxyglucose-6-phosphate present, was increased from 66 nmol.min-1.g-1 in control to 595 nmol.min-1.g-1 (P < .001) in diabetic rats. Transfer to the perfusion fluid of unlabeled D-glucose was increased (P < .001) in diabetic rats (2.32 mumol/mL) compared with control rats (0.77 mumol/mL) due to elevated (P < .001) maternal plasma glucose levels. Upon phosphorylation, 2-deoxyglucose becomes trapped within the placenta, and therefore these results indicate that all the glucose destined for direct transfer to the fetus is protected from phosphorylation while traversing the placenta, and that diabetes appears to increase placental glucose utilization, but does not induce futile cycling of glucose in an attempt to protect the fetus from an excessive influx of glucose from the mother in the rat.
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PMID:Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats. 143 91


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