Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly purified regular porcine insulin was given by portable insulin pumps through indwelling vena caval catheters to 17 (13 normal, and 4 pancreatectomized) dogs initially weighing 15 +/- 2 kg at rates ranging from 2 to 10 mU/min (total 17-250 mg) over time periods ranging from 37 to 252 days. During the course of the study, many of the animals lost weight and became anemic. Since these conditions persisted and weight loss progressed even after cessation of insulin infusion, as many of the dogs as possible (15 of 17) were autopsied for microscopic studies. Large amounts of amyloid were demonstrated in the liver, kidney, spleen, and/or pancreas in 55% (6/11) of normal, and in 75% (3/4) of pancreatectomized dogs. The amyloid deposits were Congo red positive, exhibited classical apple green fluorescence under polarized light, and possessed the characteristic ultrastructural features of amyloid. Massive deposits of amyloid were observed in animals receiving as little as 17 mg of insulin over a time span of 52 days. In those animals with hepatic amyloid, marked hepatomegaly was present (i.e., 1200 +/- 250, X +/- SD, versus 300 +/- 25 g for normal animals) and preterminal serum alkaline phosphatase levels were markedly elevated (434 +/- 285 versus 30 +/- 14 IU/L for animals without hepatic amyloid). The magnitude of the hepatic amyloid deposits precludes the possibility that they represent insulin aggregates or insulin-derived products per se. No evidence of amyloid was present in any of the tissue biopsy specimens obtained prior to insulin infusion. Moreover, the possibility that this represents an immune response to the injected porcine insulin has to be viewed in light of the fact that the amino acid sequences of dog and porcine insulins are identical. It is of particular interest that the affinity of the amyloid deposits for Congo red stain was totally abolished by prior permanganate treatment, suggesting that the amyloid was derived from serum amyloid A protein rather than from immunoglobulin light chains or insulin aggregates per se. Further evidence that the protein was of the AA-type came from the initial biochemical characterization. Gel filtration on Sephadex G100 in 6 M guanidine hydrochloride identified two small molecular weight peaks of about 13,000 and 25,000 daltons, both of which inhibited the radioimmunoassay for human AA protein.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1983 Dec
PMID:Unanticipated amyloidosis in dogs infused with insulin. 636 Jul 58

As part of a six-month prospective study of the effects of neonatal thymectomy in the spontaneously diabetic BB Wistar rat, activities of the following enzymes were determined: alkaline phosphatase (AP), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and UDP-galactosyltransferase (UDPG). In prediabetics, AP and LDH levels were higher than in sham-operated, non-diabetic controls; however, this increase was seen in nearly all diabetes-prone BB rats, diminishing the usefulness of these changes in discerning potential diabetics from asymptomatic, diabetes-prone rats. After onset of the syndrome, there was a striking elevation of AP values in all diabetics with no similar alteration in asymptomatic, diabetes-prone rats suggesting this was a diabetes-related phenomenon. By contrast, UDPG was the only enzyme to decrease immediately following the onset of the syndrome. Both UDPG and AP levels correlated with blood glucose, the former negatively and the latter positively, suggesting a close relationship with changes occurring after onset of the syndrome. The remaining enzymes increased only in a portion of diabetics alone (GOT, GPT) or in a portion of both diabetics and asymptomatic, diabetes-prone BB rats (LDH, CPK).
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PMID:Serum enzymes in the BB rat before and after onset of the overt diabetic syndrome. 643 99

Diabetes mellitus was induced in Lewis rats by streptozotocin, and these animals and control rats fed ad lib were studied after 7 weeks. At the time of sacrifice, nondecalcified histological sections of bone were prepared and subsequently quantitated by micromorphometric techniques. In addition, tibial alkaline phosphatase and mineral ash content were determined. The bones obtained from the diabetic animals are characterized by significant decrements in the quantities of osteoid and osteoclasts and by failure to acquire a tetracycline label. These histological features are attended by reduced quantities of urinary hydroxyproline and tibial alkaline phosphatase. As compared with control animals fed ad lib, diabetic rats are hyperphosphatemic and markedly hypercalciuric. Circulating alkaline phosphatase is also elevated and associated with a parallel increase in intestinal content of this enzyme. Although serum corticosterone levels are increased, diabetes is associated with decrements in both circulating immunoreactive parathyroid hormone and 1,25(OH)2D. We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover. The relative roles that functional caloric deprivation, low circulating levels of 1,25(OH)2D, hypercalciuria, hypercortisolemia, and decreased blood parathyroid hormone levels play in the genesis of these skeletal abnormalities remain to be determined.
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PMID:The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat. 645 Feb 54

The clinical characteristics of 107 patients younger than 60 years with mitral anular calcium (MAC) were compared with those of 107 age- and sex-matched control subjects. The patients with MAC included 55 men and 52 women, mean age 51 years. The control group included 55 men and 52 women, mean age 51 years. Patients with MAC had a higher prevalence of cardiomegaly on chest x-ray (p less than 0.0001), left atrial and left ventricular enlargement by echocardiography (p less than 0.0001), precordial murmurs (p less than 0.0001), diabetes mellitus (p less than 0.0001), systemic hypertension (p less than 0.025) and total conduction defects on surface electrocardiograms (p less than 0.0001) compared with the age- and sex-matched control subjects. The mean serum phosphorus and product of serum calcium and phosphorus were higher in patients with MAC (p less than 0.0025) than in the control subjects. The prevalence of coronary heart disease, aortic stenosis and hypertrophic cardiomyopathy and the mean serum cholesterol, triglyceride, total protein, albumin, creatinine, alkaline phosphatase and calcium levels were not significantly different between patients with MAC and the control subjects.
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PMID:Clinical characteristics of patients younger than 60 years with mitral anular calcium: comparison with age- and sex-matched control subjects. 650 99

The influence of diabetes on mortality and morbidity following operations for obstructive jaundice has been assessed in 118 consecutive patients, all of whom received antibiotic cover, subcutaneous heparin and intravenous mannitol. 44 patients had diabetes mellitus (37%). There were 12 post operative deaths (10%). Factors which significantly contributed to mortality included; admission values for alkaline phosphatase, creatinine, haematocrit, bilirubin and age of patient over 70 years. Although mortality was not increased in diabetics, wound sepsis was significantly more common (20% and 4% respectively; p less than 0.02). The majority of infections were due to antibiotic sensitive Staphylococcus aureus. Diabetes did not influence survival after operation for malignant disease.
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PMID:Influence of diabetes on mortality and morbidity following operations for obstructive jaundice. 669 98

The isoenzymes of canine alkaline phosphatase have been separated by isoelectric focusing on agarose gels. Alkaline phosphatase from normal tissue extracts gave heterogeneous focusing patterns with the following isoelectric points: liver pH 4.3, bone pH 4.0 to 4.9, kidney pH 4.4 to 4.7 and intestine pH 3.6 to 4.6. Plasma alkaline phosphatase isoenzymes were examined in 123 dogs with activities at least twice the normal maximum. The isoenzymes from these plasma samples had multiple bands at pH 4.3 to 4.6 but in 67 per cent of all cases, the predominant isoenzyme, named isoenzyme A, was a single band of isoelectric point pH 3.5. Isoenzyme A occurred in all dogs with diabetes mellitus or Cushing's syndrome and in 93 per cent of animals receiving steroid therapy. Increased activities of the pH 4.3 to 4.6 isoenzymes were more likely to occur in cases of hepatic degeneration.
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PMID:Isoenzymes of canine plasma alkaline phosphatase: an investigation using isoelectric focusing and related to diagnosis. 687 82

The influence of streptozotocin-induced diabetes on discrete stages of matrix-induced endochondral bone formation has been investigated. Mesenchymal cell proliferation was inhibited in diabetic rats as evidenced by a 65% reduction of ornithine decarboxylase (ODC) activity and a 56% reduction of [3H]thymidine incorporation per microgram DNA compared to nondiabetic controls; the inhibition was prevented by insulin treatment. In diabetic animals, chondrogenesis on day 7 was reduced by 49% compared to control animals as assessed by 35SO4 incorporation. Exogenous insulin was stimulatory to cartilage development when present during days 0 through 4 (mesenchymal cell proliferation). Calcification of cartilage and osteogenesis were reduced by more than 50% in diabetic rats and corrected by insulin as measured by alkaline phosphatase activity and 45Ca incorporation. Decreased in vivo endochondral bone growth and development during diabetes is the result of 1) inhibition of insulin-dependent mesenchymal cell proliferation, 2) decreased and delayed cartilage formation due to impaired mesenchymal cell proliferation, 3) decreased and delayed vascular invasion prior to chondrolysis and osteogenesis, and 4) reduced insulin-dependent calcification and ossification.
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PMID:Influence of experimental diabetes and insulin on matrix-induced cartilage and bone differentiation. 698 62

Biochemical and bone scintigraphic studies were performed in nondiabetic and diabetic patients receiving hemodialysis at the time of kidney transplantation to assess the degree of secondary hyperparathyroidism. Despite lower serum calcium concentrations, diabetic patients had significantly lower parathyroid hormone (PTH) levels than nondiabetic patients. In addition, diabetic patients had lower graded total-skeletal scintigraphic scores than nondiabetic patients. The PTH levels showed positive correlations with bone scan scores and with alkaline phosphatase in nondiabetic patients but not in diabetic patients. Avascular necrosis occurred in 17% of nondiabetic patients and in only 2% of diabetic patients. Patients with avascular necrosis had significantly higher PTH levels than patients without avascular necrosis. Diabetes mellitus seems to confer a protective effect from the skeletal manifestations of secondary hyperparathyroidism, including avascular necrosis.
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PMID:Decreased secondary hyperparathyroidism in diabetic patients receiving hemodialysis. 700 80

To assess the relationship between the decreased bone mass observed in young insulin-requiring diabetic patients and vitamin D metabolism, we measured serum 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D concentration in 45 white, insulin-dependent diabetic subjects, 7-18 yr of age. Metacarpal cortical thickness in 87% of these diabetics was below the mean for their respective ages, while 16% had a cortical thickness value greater than 2 sDs below the mean. Serum calcium and phosphate concentrations were normal, immunoreactive parathyroid hormone was in the low normal range, and total serum alkaline phosphatase was elevated compared to age- and sex-matched controls. Circulating 24,25-dihydroxyvitamin D concentrations were significantly elevated, and 1,25-dihydroxyvitamin D was significantly decreased. The increase in 24,25-dihydroxyvitamin D was greater in the diabetics with the most severe bone loss and was maximally increased during the first 5 yr of clinical diabetes. No apparent correlation was seen between metabolic control, as measured by hemoglobin A1C and urine and plasma glucose, and the circulating levels of the vitamin D metabolites. Despite appropriate insulin replacement, alterations in vitamin D metabolism occur in the young insulin-dependent diabetic and could relate to the decrease in cortical bone mass observed in these patients.
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PMID:Alterations in circulating vitamin D metabolites in the young insulin-dependent diabetic. 702 72

Alterations in circulating alkaline phosphatase have been described in both man and the experimental animal with chronic insulin deficiency. We evaluated plasma and tissue alkaline phosphatase levels in freely-fed control, streptozotocin-induced diabetic and insulin-treated diabetic rats, seven weeks after the induction of diabetes. Circulating alkaline phosphatase activity was markedly elevated in the insulin deficient animal (p less than 0.001) and completely normalized following insulin administration. The elevated plasma alkaline phosphatase activity observed in the insulin deficient animals was heat-resistant and phenylalanine-sensitive, a pattern typical of the intestinal isoenzyme. Small intestinal alkaline phosphatase activity was significantly higher (p less than 0.01) in the diabetic animals, but comparable in the insulin-replaced and control rats. The intestinal isoenzyme activity was found to be strikingly insulin-sensitive; withholding insulin therapy for 36 hr prior to sacrifice resulted in an abrupt rise in both plasma and intestinal alkaline phosphatase values comparable to those observed in the insulin-deficient state. In contrast to these observations, skeletal alkaline phosphatase activity was decreased in the insulin deficient animal (p less than 0.01) and this abnormality was corrected by insulin replacement. Neither insulin deficiency nor insulin replacement resulted in any significant changes in the hepatic alkaline phosphatase isoenzyme.
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PMID:Alkaline phosphatase activity in chronic streptozotocin-induced insulin deficiency in the rat: effect of insulin replacement. 703 17


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