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)

The pseudotetrasaccharide acarbose, previously known as a potent inhibitor of intestinal alpha-glucoside hydrolases, was investigated with regard to its influence on islet lysosomal enzyme activities and the insulin secretory processes. We observed that acarbose was a potent inhibitor of mouse islet lysosomal acid glucan-1,4-alpha-glucosidase activity, EC50 approximately 5 mumol/l, as well as of acid alpha-glucosidase activity. In contrast, acarbose did not influence other lysosomal enzyme activities such as acid phosphatase and N-acetyl-beta-D-glucosaminidase. Neutral alpha-glucosidase (endoplasmic reticulum) was only moderately inhibited in homogenate and was unaffected in intact islets. Incubation of isolated mouse islets with acarbose revealed that the pseudotetrasaccharide was a strong inhibitor of glucose-induced insulin secretion, EC50 approximately 500 nmol/l, and a significant inhibition was already observed at a concentration of acarbose as low as 100 nmol/l. The acarbose analogue maltotetrose did not influence either glucose-induced insulin release or islet lysosomal enzyme activities. Further, acarbose as well as two other alpha-glucoside hydrolase inhibitors, the deoxynojirimycin derivatives miglitol and emiglitate, did not affect islet glucose oxidation at low or high glucose levels. Acarbose also inhibited insulin release induced by the sulfonylurea glibenclamide, whereas insulin secretion stimulated by the cholinergic muscarinic agonist carbachol or the phosphodiesterase inhibitor isobutylmethylxanthine was unaffected by the drug. Moreover, complementary in vivo experiments showed that pretreatment of mice with acarbose to allow for endocytosis of the compound markedly suppressed the insulin secretory response to an intravenous glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Jul
PMID:The pseudotetrasaccharide acarbose inhibits pancreatic islet glucan-1,4-alpha-glucosidase activity in parallel with a suppressive action on glucose-induced insulin release. 778 51

Glurenorm, a IInd generation sulfanylurea preparation, was used for a year as a sugar-reducing drug in 20 patients with non-insulin-dependent diabetes mellitus and concomitant diseases of the liver (cirrhosis, chronic hepatitis, n = 5) and biliferous duct (cholelithiasis, a state following cholecystectomy, chronic cholecystitis, n = 15). A year follow-up has not shown deterioration of liver function as indicated by results of liver tests (AST, ALT, acid phosphatase, gamma-glutamyltranspeptidase, bilirubin, cholesterol, triglycerides). The hypoglycemic effect of the drug proved to be inferior to that of sulfanylurea derivatives, but the absence of side effects permit higher doses of glurenorm (up to 4-6 tablets daily) as against other oral sugar-reducing drugs.
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PMID:[Glurenorm in the treatment of patients with non-insulin-dependent diabetes mellitus with diseases of the liver and bile ducts]. 841 21

The activity of all principal groups of lysosomal enzymes (acid phosphatase, lipase, beta-galactosidase, sulphatase and cathepsin B) was measured in the visual cortex of rabbits with experimental diabetes. In the first stage of diabetes (21 days), it was observed that enzyme activities in the free fraction and in the membrane-bound fraction are decreased as compared to the initial values determined in healthy animals. In the later stages of diabetes (90-180 days), all lysosomal enzyme activities increased except for sulphatase. This indicated a superiority of catabolic processes in visual cortex cells in the course of experimental diabetes.
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PMID:The activity of lysosomal enzymes in visual cortex of rabbits during experimental diabetes. 870 84

Low-molecular-weight acid phosphatase (ACP1) is a polymorphic protein-tyrosine phosphatase present in all human tissues, including adipocytes. A positive association between the low-activity ACP1*A/*A genotype and extreme body mass index has previously been shown by us in obese subjects from the population of Rome. We have now studied a sample of 265 subjects with non-insulin-dependent diabetes mellitus (NIDDM) from another Italian population. There is a significant interaction between ACP1, body mass index, and blood lipid level. A highly significant positive association between ACP1*A/*A and high body mass index similar to that previously observed in obese subjects from the population of Rome is present only in those NIDDM subjects with blood lipid levels within the normal range. In NIDDM subjects the low-activity ACP1*A/*A variant seems to favor the increase of body mass or blood lipid levels or both. The pattern of association is independent of sex, age at survey, age at onset of diabetes, duration of disease, and therapy.
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PMID:Low-molecular-weight acid phosphatase (ACP1), obesity, and blood lipid levels in subjects with non-insulin-dependent diabetes mellitus. 919 10

In order to investigate the pathogenic role of bone resorption by osteoclasts in altered bone metabolism in non-insulin-dependent diabetes mellitus (NIDDM), the circulating levels of tartrate resistant acid phosphatase (TRACP) were simultaneously determined with osteocalcin, in rat models of NIDDM, i.e., genetic Wistar fatty rats and neonatally streptozotocin-induced diabetic rats (NSZ rats). In Wistar fatty rats exhibiting hyperglycemia and hyperinsulinemia, plasma TRACP was 40.0+/-0.4 U/l (mean+/-SE), significantly higher than that of 32.8+/-1.3 U/l in their lean littermates (p < 0.01). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats (p < 0.02-0.001). On the other hand, plasma TRACP in NSZ rats was 13.6+/-1.0 U/l, significantly lower than that of 31.4+/-1.2 U/l in their controls (p < 0.01). In addition, there were positive correlations between circulating TRACP and insulin levels in both NIDDM rat models (p < 0.05-0.01). Furthermore, plasma osteocalcin levels in these NIDDM models were significantly decreased than those of their corresponding controls (p < 0.001). Consequently, in Wistar fatty rats with hyperinsulinemia, it is suggested that the bone formation by osteoblasts was decreased, while the bone resorption by osteoclasts was increased. In contrast, in NSZ rats with hypoinsulinemia, both of bone formation and resorption were speculated to be decreased, indicating the decreased bone turnover. These results suggest that, although the deterioration in the osteoblastic function can be commonly observed in NIDDM animal models, the osteoclastic function is heterogeneous under NIDDM conditions.
J Diabetes Complications
PMID:Circulating levels of tartrate-resistant acid phosphatase in rat models of non-insulin-dependent diabetes mellitus. 961 74

In order to clarify the degradation of elastin under abnormal conditions, we examined the aortic elastolytic activity in rat experimental diabetes mellitus induced by treatment with streptozotocin and in rat experimental aneurysm induced by treatment with an inhibitor of lysyloxidase (beta-aminopropionitrile: BAPN). Measurement of the aortic elastolytic activity used 14C-labeled elastin as the substrate, and the determined value was compared with the aortic lysosomal enzyme (acid phosphatase) activity. In the case of experimental diabetes, the aortic elastolytic activity was not changed, but the aortic acid phosphatase activity was significantly increased compared with the control. In the case of the experimental aneurysm, the aortic elastolytic activity measured after 2 and 3 weeks was increased compared with each control. There was a negative correlation (r=-0.435, n=36) between the elastolytic activity and the cross-linking (desmosine) content in the aorta. The ratio of elastolytic activity to desmosine content was significantly increased compared with the control. Therefore, the degradation of aortic elastin in the experimental aneurysm was caused by elastase, not by lysosomal enzymes. We concluded that an elastase-like enzyme mainly contributed to the degradation of elastin in the experimental aneurysm since the inhibitory pattern of the elastolytic activity in the experimental aneurysm was similar to that of pancreatic elastase.
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PMID:Comparison of elastolytic activity between experimental aneurysm and experimental diabetes mellitus. 970 67

One of the classic histologic forms of renal osteodystrophy is osteitis fibrosa, and its distinguishing characteristic is bone marrow (BM) fibrosis, caused by the activation of marrow parenchymal cells. A bone biopsy must be performed in order to establish the diagnosis of renal osteodystrophy. The clinical use of bone biopsy is restricted, however, due to the invasiveness of the procedure. In recent studies, bone scans have provided information useful for the differential diagnosis between osteomalacia and osteitis fibrosa. However, bone scans can not provide information on the bone marrow status. Bone marrow immunoscintigraphy (BMIS) using Tc-99m anti-granulocyte antibody (AGA), a highly sensitive test for the detection of bone marrow abnormalities which is also a noninvasive method, has rarely been reported in chronic renal failure (CRF). BMIS can provide information in patients with myelofibrosis. The purpose of this study was to evaluate the usefulness of BMIS in CRF patients with special regards to biochemical parameters. Nineteen CRF patients (13 men, 6 women; mean age: 48 +/- 11 years) in whom bone scintigraphy using Tc-99m MDP (methylene diphosphonate) showed the so-called superscan pattern were included in the study. Their primary renal diseases were chronic glomerulonephritis (n = 14), diabetes (n = 4), and polycystic kidney disease (n = 1). Modes of therapies were continuous ambulatory peritoneal dialysis (CAPD) (n = 13; mean duration: 9.5 months), HD (n = 5; mean duration: 7.8 months), and conservative treatment (n = 1). BMIS using Tc-99m labeled anti-granulocyte monoclonal mouse antibody BW250/183 was performed, and the results were compared with the biochemical parameters of the patients. According to the presence of BM expansion, which may represent marrow fibrosis, the 19 patients were divided into two groups: Group I (n = 7) with BM expansion and Group II (n = 12) with normal marrow distribution. The biochemical parameters and bone markers of Group I were compared with those of Group II. There was no significant difference in biochemical parameters (blood hemoglobin, serum ferritin, erythropoietin, BUN, creatinine) between the two groups. There were no significants difference in serum calcium, phosphorus, tartate-resistant acid phosphatase (TRAP), and intact parathyroid hormone (iPTH) between the two groups. Serum alkaline phosphatase (ALP) and osteocalcin were significantly (P < 0.05) higher in Group I than in Group II. These results suggest that patients with bone marrow expansion in BMIS have increased levels of ALP and osteocalcin, indicating an increased osteoblastic activity. BMIS may be useful for the detection of bone marrow expansion due to marrow fibrosis in renal osteodystrophy, and for the evaluation of the extent of bone marrow fibrosis.
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PMID:Bone marrow immunoscintigraphy (BMIS): a new and important tool for the assessment of marrow fibrosis in renal osteodystrophy? 1064 20

Tinospora cordifolia is widely used in Indian Ayurvedic medicine for treating diabetes mellitus. Oral administration of an aqueous T. cordifolia root extract (TCREt) to alloxan diabetic rats caused a significant reduction in blood glucose and brain lipids. The extract caused an increase in body weight, total haemoglobin and hepatic hexokinase. The root extract also lowers hepatic glucose-6-phosphatase and serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in diabetic rats. Thus TCREt has hypoglycaemic and hypolipidaemic effect.
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PMID:Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats. 1072 Jul 84

The ability of insulin to influence activities of various protein kinases and protein phosphatases, that are thought to mediate insulin action, are limited in patients with insulin resistance. Because numerous responses to insulin are affected, we undertook studies to determine whether protein tyrosine phosphatases (PTPs) activities are altered in patients with diabetes syndrome. In order to evaluate abnormal PTP activities, we done a comparative study using erythrocytes from normal and diabetic patients. We determined the activity of the cytosolic acid PTP in basal and insulin-dependent states. Mean basal PTP activities, were found to be significantly higher in diabetics than in normal subjects (type 1 diabetics: 0.36 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g hemoglobin (Hb), P < 0.001; type 2 diabetics: 0.35 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g Hb, P < 0.001). Insulin, at concentrations above physiological levels (1 mIU/ml), inhibited the PTP activities in erythrocytes from normal subjects (-15 +/- 4.1%, P < 0.01). Insulin could also modulate glycolysis, probably as a consequence of receptor tyrosine kinase activation, inducing phosphorylation of protein band 3 and hence the release of glycolytic enzymes. We have previously reported that a reductase enzyme in human erythrocytes is dependent on glycolysis being significantly activated (+28 +/- 3.1%, P < 0.001) by high insulin levels (1 mIU/ml). Mean basal reductase activities were found to be significantly lower in diabetics than in normal subjects (type 1 diabetics: 0.77 +/- 0.03 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001; type 2 diabetics: 0.77 +/- 0.04 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001), indicating altered erythrocyte metabolism in the diabetic patients. High glucose levels were used to mimic hyperglycemia condition, using erythrocytes from normal subjects. At 30 mM glucose, erythrocytic phosphatase activity was stimulated (+32 +/- 4.2%, P < 0.0001), although no effect was observed on the reductase enzyme at the same glucose levels. Results indicated that diabetic disorders appear to be associated with quantitative alterations of erythrocyte acid phosphatase activity and other enzymes that depend on the glycolytic rate (reductase). The overall data suggest that erythrocyte acid phosphatase may have a role in the modulation of glycolytic rates through the control of insulin receptor phosphorylation.
Diabetes Res Clin Pract 2000 Mar
PMID:Insulin and high glucose modulation of phosphatase and reductase enzymes in the human erythrocytes: a comparative analysis in normal and diabetic states. 1074 68

The aim of this study was to establish and quantify changes in the activities of the some lysosomal enzymes and to determine the type of changes in the ultrastructure of the submandibular gland in rabbits caused during progression of diabetes. The experiment was conducted on 89 New Zealand rabbit males. Diabetes was induced by the intravenous administration of 10% alloxan solution at a dose of 10-mg/kg-body weight. On the seventh day after alloxan administration, the level of glucose in blood was determined. Rabbits were divided into five groups: intact (n=18), 21-day diabetes (n=18), 42-day diabetes (n=17), 90-day diabetes (n=19) and 180-day diabetes (n=17). From killed animals in each group, the submandibular glands were removed and fixed or stored. Enzyme activities were assayed by spectrophotometric methods using substrates (Sigma) which release 4-methyloumbeliferol when they react with the proteases. Fixation procedure was done according to standard methods. Semi-thin and ultra-thin specimens were prepared by use of clearly visible after 42 days of diabetes. Mitochondria were damaged, accumulation of large amounts of lipids in the intracellular spaces was observed. After 90 days the presence of vacuoli and swollen lysosomes were observed, some cells also contained myelin figures. After 180 days the greatest changes were observed in the blood vessels, which had thickened walls and were often occluded. We concluded that the total activity of acid phosphatase and beta-N-acetyl-glucosaminidase in the submandibular gland was correlated with the level of glucose but there was no correlation between total beta-galactosidase activity and the serum concentration level of glucose has been detected during course of diabetes. The activities of the free fractions of acid phosphatase, beta-galactosidase and beta-N-acetyl-glucosaminidase in the submandibular gland were higher than the bound fractions in all groups of rabbits. The changes in the ultrastructure of the submandibular gland were correlated with changes in serum glucose level and with lysosomal enzymes activities during progression of experimental diabetes in rabbits.
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PMID:Changes in the activity of some lysosomal enzymes and in the fine structure of submandibular gland due to experimental diabetes. 1074 71


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