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)

Diabetes mellitus is associated with enhanced passive intestinal uptake of cholesterol and fatty acids. In order to determine the basis for these changes in intestinal permeability, the jejunal morphology and the lipid content of purified brush border membranes (BBM) were measured in fasted and fed control (C) and streptozotocin diabetic (DM) rats. There was no difference between C and DM in BBM sucrase or alkaline phosphatase; fasting had no effect on BBM enzymes in C, but in DM fasting was associated with increased sucrase activity per length of jejunum. In C fasting was associated with higher levels of BBM total phospholipid, lecithin, choline and amine phospholipids, whereas fasting in DM was associated with higher BBM cholesterol and lower free fatty acids. In the fasting DM, there was a greater villus and mucosal surface area than in the fasting C. A previous study demonstrated that with fasting in DM versus C, cholesterol uptake was unchanged, but when animals were fed, cholesterol and fatty acid uptake were greater into the jejunum of fed DM as compared with fed C. In the BBM of fed DM as compared with C, there was a significant increase in total phospholipid, lecithin, phosphatidyl ethanolamine, choline and amine phospholipids, and phospholipid/cholesterol ratio. Thus, (1) fasting is associated with changes in intestinal morphology, BBM lipids; (2) the effect of fasting is different in DM and C; (3) the enhanced uptake of lipids into the jejunum of fed diabetic rats is not due to changes in villus morphology, but may be due to alterations in the BBM phospholipids.
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PMID:Intestinal brush border membrane marker enzymes, lipid composition and villus morphology: effect of fasting and diabetes mellitus in rats. 286 16

Alterations in ouabain inhibitable Na-K ATPase activity, polyol pathway activity, and myoinositol metabolism are part of a unifying hypothesis proposed to explain the pathogenesis of the chronic complications of diabetes mellitus. Direct measurements of renal ouabain inhibitable Na-K ATPase activity in animals with streptozotocin-induced diabetes show increased or decreased activity, depending on the nephron segment examined and the duration of diabetes. While myoinositol feeding corrects depressed Na-K ATPase activity in peripheral nerve of streptozotocin diabetic rats, the effect of myoinositol feeding on altered renal Na-K ATPase activity is unknown. To assess the effect of experimental diabetes on renal ouabain inhibitable Na-K ATPase activity and test the involvement of the polyol/inositol pathway, we assayed kidneys from normal, streptozotocin diabetic, and myoinositol-supplemented diabetic rats for renal ouabain-inhibitable Na-K ATPase, alkaline phosphatase, and tau-glutamyltranspeptidase (tau-GT) activity. Ouabain inhibitable Na-K ATPase activity, expressed per milligram of protein, is increased in the inner medulla of the diabetic kidney compared with normal and, expressed per microgram DNA, is increased in both the inner medulla and cortex. Myoinositol supplementation did not affect the increase in renal enzyme activity seen with streptozotocin diabetes. These observations suggest that the regulation of renal ouabain inhibitable Na-K ATPase activity, in streptozotocin diabetes, does not depend on supplemental myoinositol. These findings do not exclude the possibility that changes in polyol or myoinositol concentrations in a specific nephron segment may have pathogenetic significance for diabetic nephropathy.
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PMID:Renal ouabain inhibitable Na-K ATPase activity and myoinositol supplementation in experimental diabetes mellitus. 289 13

Radiographs of the hands and feet of 19 diabetic patients with severe neuropathy were compared to those of 22 control patients without neuropathy. The two groups were matched for age, sex, and duration of diabetes. Cortical bone mass, measured by x-ray morphometry, was significantly lower in both the hands (p less than 0.002) and the feet (p less than 0.001) of those with neuropathy. The osteopenia was worse in the feet than the hands and also worse in women. Serum alkaline phosphatase levels were also significantly higher in the neuropathy group (p less than 0.005). Metatarsal fractures were a frequent finding in the neuropathic patients, but were not seen in controls. The presence of metatarsal fractures was strongly associated with the subsequent development of diabetic osteopathy (p less than 0.001). We conclude that cortical bone mass in the feet and hands is reduced in severe diabetic neuropathy. This may contribute to the predisposition to metatarsal fracture and diabetic osteopathy.
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PMID:Osteopenia and metatarsal fractures in diabetic neuropathy. 295 Nov 18

This study investigates the diabetes-induced lesions in liver and kidney and in addition the possible side effects of the diabetogenic substance streptozotocin (SR) on these organs in non-diabetic animals. 5-week-old female Wistar rats were injected 65 or 130 mg SR/kg body mass. Some animals of the drug group did not become hyperglycemic; thus it was possible to separate the drug effect from the diabetic influence on liver and kidney. In serum investigations some metabolic changes concerning the activities of the liver enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and the concentrations of urea and creatinine up to 30 days after drug application were studied. SR in hyperglycemic animals causes a time and dose dependent rise in all investigated parameters. Also in normoglycemic rats a significant increase in alkaline phosphatase and in creatinine was observed after 10 days. After 21 and 30 days there were no differences compared to untreated control rats, whereas elevated levels were observed in the hyperglycemic rats. Thus our results support the view of a short damaging effect of SR on liver and kidney without inducing a diabetic state; in hyperglycemic rats the damaging effect is more pronounced.
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PMID:Effect of streptozotocin on transaminases, creatinine and urea in serum of rats. 297 78

We have studied the cytosolic estrogen receptor in uterus of rats after castration and diabetes induction with Streptozotocin, and the relationship of estradiol (E2) binding with phosphatase activities. Ovariectomy (OVX) and diabetes produced a significant reduction in Type I and II binding sites, but did not affect the equilibrium dissociation constants. The reduction of receptor levels was partially reversed by homogenization and incubation with 20 mM molybdate (MoO4) and also by chronic treatment with E2. Considering the possibility that the increase in E2 binding in the presence of MoO=4 was due to phosphatase inhibition, the activities of these enzymes hypothetically involved in receptor dephosphorylation and inactivation were determined in uterine homogenate and cytosol from intact, OVX, and diabetic rats with and without E2 treatment. Chronic OVX and diabetes induced stimulation of alkaline, acid and neutral phosphatase activities. On the contrary, the increment of estrogenic receptors due to E2 treatment was not correlated with changes in phosphatase activity. It is possible that this effect was due to the protection of the receptor or to the induction of receptor synthesis by E2. Molybdate inhibited acid and neutral phosphatases and increased alkaline phosphatase, which suggest that neutral and acid phosphatases are identical and that they were responsible for the receptor inactivation. However, it is unclear at present the relationship between the increment of alkaline phosphatase and the reduction of receptors.
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PMID:Estradiol binding and phosphatase activity in the uterus after castration and chronic diabetes: effect of molybdate and estrogen replacement. 300 2

Recent evidence suggests that the protein osteocalcin is like the bone alkaline phosphatase produced by osteoblasts and circulates in human blood. With the introduction of a radioimmunoassay for serum osteocalcin it was hoped that this test would provide a useful index of altered bone metabolism. Therefore serum osteocalcin was measured in 88 controls and 112 patients with disorders of calcium and phosphate metabolism, isolated elevation of alkaline serum phosphatase in the absence of disease (isolated hyperphosphatasaemia) and children prone to osteopenia. In the controls serum osteocalcin was higher in children less than 15 years (median and range: 11.9, 7.7-15.3 ng/ml) than in adults (3.7, 2.6-5.2 ng/ml) and was highly correlated to alkaline serum phosphatase activity (r = 0.87, n = 88, P less than 0.01). Osteocalcin was elevated in primary hypoparathyroidism, low in untreated hypoparathyroidism but normal in hypoparathyroidism (including pseudohypoparathyroidism) during vitamin D treatment. The bone protein was low-normal and increased to high-normal levels during vitamin D therapy in vitamin D deficiency rickets and familial hypophosphataemic rickets, but remained low in patients with end organ resistance to 1,25-dihydroxyvitamin D. Osteocalcin (and urinary hydroxyproline) were not elevated in isolated hyperphosphatasaemia, indicating that mechanisms other than increased bone turnover may account for the markedly elevated serum alkaline phosphatase activity in these subjects. Osteocalcin was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. It is concluded that the measurement of serum osteocalcin seems to be a reliable index of bone formation provided that the vitamin D status and renal function are normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of serum osteocalcin as an index of altered bone metabolism. 301 28

We investigated immunohistochemically the phenotypes of mononucleated cells invading pancreatic islets of diabetic BB/OK rats in comparison to the diabetes-resistant parental strain, and 12 and 120 days after a temporary treatment (10 days) with a monoclonal antibody (1 mg/kg b.w.) directed against interleukin 2 receptor (IL 2R) combined with a subtherapeutic dose of cyclosporin A (1.5 mg/kg b.w.). Using a panel of monoclonal antibodies (OX-19, OX-8, W3/25, KI-M2R, OX-6, OX-17, ART-18) and the alkaline phosphatase anti-alkaline phosphatase system to visualize the bound primary antibodies, we observed an even distribution of mononucleated cells across the endocrine pancreas at a "background" level when obtained from diabetes-resistant parental rat strain. Diabetic BB/OK rats, characterized by a moderate hyperglycemia and a marked decrease of pancreatic insulin content, displayed a remarkable accumulation of mononucleated cells in the endocrine pancreas. Morphometric studies revealed an increase of all phenotypes investigated, nearly all mononucleated cells expressed class II histocompatibility antigens (OX-6+, OX-17+) and the number of cells expressing the IL 2R (ART-18+) was markedly enhanced. Sixty-seven percent of the immunotherapeutically treated BB/OK rats normalized plasma glucose and enhanced pancreatic insulin content. The successfully treated animals are characterized by a decrease of cells invading pancreatic islets (OX-19+, OX-8+, W3/25+, KI-M2R+), a decrease of class II histocompatibility antigen and IL 2R expression. The number of IL 2R cells is also diminished in the endocrine pancreas of unsuccessfully treated BB rats.
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PMID:Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: effect of interleukin 2 receptor-targeted immunotherapy. 306 88

In the present study bone mineral content (BMC) was measured at 1/3 and 1/10 the length of the radius from the distal end in 100 adult diabetic subjects (55 females, 45 males, 54 insulin-dependent [IDD], 46 non-insulin-dependent [NIDD]), using single photon absorptiometry. Each individual BMC value in the diabetics was first compared to normal BMC values for age obtained in our laboratory from 500 non-diabetic subjects. BMC in the diabetics was within the normal range (M +/- 2 SD) with respect to sex and age. Data from IDD and NIDD males, under and over 50 years of age, and of IDD and NIDD females, pre- and postmenopausal, were compared with the respective control group data after matching each diabetic subject to a non-diabetic one of identical age and menstrual history and of comparable body mass index. In each group BMC in the diabetic subjects was found not to be statistically different from BMC in the control ones. Correlation analysis was carried out between BMC and endocrine or metabolic parameters obtained in 52 of the diabetic patients. BMC in diabetic subjects was not correlated with plasma levels of hormones (thyroid hormones, cortisol, 17-beta-estradiol, testosterone), Ca, P or alkaline phosphatase activity. It was inversely correlated with urinary Ca and P in NIDD women and with urinary Ca in NIDD men. No relationship was found between BMC and the metabolic control of diabetes (evaluated by basal glycemia, 2h-post-prandial glycemia and glycosylated hemoglobin).
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PMID:Bone mineral density in diabetes mellitus. 325 88

Bone disease related to aluminum toxicity (aluminum-related bone disease) presents with variable clinical and biochemical findings in patients with renal failure. Bone pain and muscle weakness are common, although afflicted patients can be asymptomatic. Bone pain can be generalized or localized to the hips, back, feet, or ankles; proximal muscle weakness is common. Most cases in the United States arise from the ingestion of aluminum-containing gels by patients on long-term dialysis treatment. Patients at increased risk for developing aluminum-related bone disease include those with earlier parathyroidectomy, failed renal transplant, previous bilateral nephrectomy, and diabetes mellitus. Biochemical features that are common with aluminum-related bone disease include plasma aluminum levels greater than 100 to 150 micrograms/L, serum parathyroid hormone (PTH) levels equal to or lower than those in dialysis patients without bone disease, and normal or slightly elevated serum calcium levels. Plasma alkaline phosphatase levels are often elevated. In our experience, microcytic anemia has been uncommon. An increase in plasma aluminum levels greater than 200 micrograms/L 24 to 48 hours after the infusion of the chelating agent deferoxamine (DFO) correlates with an increased bone aluminum content, and an increment greater than 400 micrograms/L suggests marked aluminum accumulation. Radiographs are usually nonspecific. When results from indirect diagnostic procedures are equivocal, a bone biopsy is necessary. After a diagnosis of aluminum-related bone disease is established, therapy with DFO may be useful. DFO increases both the total plasma aluminum level and its ultrafilterable fraction. After an infusion of DFO, the removal of aluminum increases from 50 to 300 micrograms to 4 to 8 mg per dialysis session. Aluminum removal is similar during continuous ambulatory peritoneal dialysis after either intravenous (IV) or intraperitoneal (IP) administration of DFO. Usually, 2 to 4 g of DFO is administered once weekly, but the optimal dose and duration of therapy have not been determined. Symptoms usually improve after 4 to 12 weeks, and bone biopsies show improvement after treatment for 6 to 12 months. Further experience with DFO is needed, both to identify the optimal dosage and to clarify the risks of long-term therapy in patients with renal failure.
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PMID:Diagnosis of aluminum-related bone disease and treatment of aluminum toxicity with deferoxamine. 329 88

The EXPERT consultation system-building tool, a knowledge-based artificial intelligence program developed at Rutgers University, has been applied to the development of a laboratory consultation system facilitating sequential laboratory testing and interpretation. Depending on the results of a basic panel of laboratory tests, the system requests that specific secondary tests be performed. Input of these secondary findings can result in requests for tertiary testing, to complete the database necessary for interpretation. Interpretation of all results is based upon final inferences from the collected findings through a series of rules, a hierarchical network that yields an efficient production system not easily obtained through conventional programming. The rules included in this model are based upon initial results for total protein, calcium, glucose, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, thyroxin, hemoglobin, mean corpuscular volume, and the concentrations of four drugs. Pertinent clinical history items included are jaundice, diabetes, thyroid disease, medications, and ethanol. Implementing this system in a laboratory-based accelerated testing program involving outpatients maximized the effective use of laboratory resources, eliminated useless testing, and provided the patient with low-cost laboratory information.
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PMID:Application of the EXPERT consultation system to accelerated laboratory testing and interpretation. 352 78


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