Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the relation between activities of islet glycogenolytic alpha-glucosidehydrolases and insulin secretion induced by glucose and 3-isobutyl-1-methylxanthine (IBMX) by means of suppressing 1) insulin release (Ca2+ deficiency) and 2) islet alpha-glucosidehydrolase activity (selective inhibition by the deoxynojirimycin derivative miglitol). Additionally, the in vivo insulin response to both secretagogues was examined. We observed that, similar to glucose-induced insulin release, islet glycogenolytic hydrolases (acid amyloglucosidase, acid alpha-glucosidase) were highly Ca2+ dependent. Acid phosphatase, N-acetyl-beta-D-glucosaminidase, or neutral alpha-glucosidase (endoplasmic reticulum) was not influenced by Ca2+ deficiency. In Ca2+ deficiency IBMX-induced insulin release was unaffected and was accompanied by reduced activities of islet alpha-glucosidehydrolases. Miglitol strongly inhibited glucose-induced insulin release concomitant with a marked suppression of islet alpha-glucosidehydrolase activities. Direct addition of miglitol to islet homogenates suppressed acid amyloglucosidase [half-maximal effective concentration (EC50) approximately 10(-6) M] and acid alpha-glucosidase. Acid phosphatase and N-acetyl-beta-D-glucosaminidase were unaffected. The miglitol-induced inhibition of glucose-stimulated insulin release was dose dependent (EC50 approximately 10(-6) M) and displayed a remarkable parallelism with the inhibition curve for acid amyloglucosidase. The in vivo insulin secretory response to glucose was markedly reduced in dystrophic mice (low amyloglucosidase), whereas the response to IBMX was unaffected. In summary, islet glycogenolytic hydrolases are Ca2+ dependent, and acid amyloglucosidase is directly involved in the multifactorial process of glucose-induced insulin release. In contrast the mechanisms of IBMX-stimulated insulin secretion operate independently of these enzymes. The effects of miglitol, a drug currently used in diabetes therapy, deserves further investigation.
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PMID:Ca2+ deficiency, selective alpha-glucosidehydrolase inhibition, and insulin secretion. 768 25

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)
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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

The expression of some faecal hydrolytic enzymes in rats fed for 4 months on sucrose or starch enriched diets was compared with a standard diet. The assay reliability was confirmed for animal and experimental variability. The beta-D-glucuronidase and beta-D-glucosidase activities were always higher in rats fed on starch than on other diets. N-acetyl-beta-D-glucosaminidase and N-acetyl-beta-D-galactosaminidase showed decreased activity when passing from a standard to a sucrose, and from a sucrose to a starch diet. There was little modification in the levels of faecal alpha-D-glucosidase, sulphatase and protease with the various experimental diets.
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PMID:Carbohydrate enriched diets and bacterial glycosidases in rat faeces. 830 95

In previous investigations we have shown a striking relationship between the activity of glycogenolytic glucose producing acid hydrolases in pancreatic islet tissue and certain insulin-releasing processes. In the present investigation we have studied the relation between islet lysosomal enzyme activities and glucose-induced insulin secretion in vitro in the presence of various insulin secretory inhibitors. It was observed that the nonmetabolizable glucose analogue, mannoheptulose (5 mmol/l) did induce a 2-fold increase in insulin release at low (1 mmol/l) glucose, and a total suppression of insulin release at high (16.7 mmol/l) glucose. These changes in the insulin-secretory pattern were accompanied by similar changes in the activity of islet acid alpha-glucosidase. The activities of neutral alpha-glucosidase (endoplasmic reticulum) or acid phosphatase and N-acetyl-beta-D-glucosaminidase (lysosomes) were not affected by mannoheptulose. 2-Deoxyglucose (5 mmol/l), another glucose analogue, did not increase insulin secretion or acid alpha-glucosidase activity at low glucose. At high glucose, however, a partial inhibition of both insulin release (approximately 50%) and acid alpha-glucosidase activity was seen. 2-Deoxyglucose slightly suppressed acid phosphatase activity but did not influence the activities of neutral alpha-glucosidase or N-acetyl-beta-D- glucosaminidase. Direct addition of glucose to islet homogenates showed a suppressive effect on alpha-glucosidase activity at pH 4.0 and 5.0. The glucose analogues displayed only marginal (-10%) inhibition of alpha-glucosidase activity at pH 5.0. No effect of the analogues was seen at pH 4.0.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Islet lysosomal enzyme activities and glucose-induced insulin secretion: effects of mannoheptulose, 2-deoxyglucose and clonidine. 844 62

The levels of some enzymes of lysosomal origin were assayed during days 2 and 5 of life in plasma from 11 sets of twin neonates and from 25 neonates from single pregnancies (13 of weight appropriate for gestational age and 12 small for their gestational age) as controls. The plasma enzyme levels were also determined in the correspondent twin and control mothers 2 days after delivery. N-Acetyl-beta-D-glucosaminidase isoenzymes were assayed after chromatofocusing separation. All the plasma enzyme levels were higher in the group of twin neonates and of their mothers than in the respective control groups with differences highly statistically significant for two enzymes, beta-D-galactosidase and alpha-D-glucosidase. In neonate plasma lysosomal enzymes are increased at the fifth day of life with respect to the second day. Full term control neonates showed the same enzyme trend. For the N-acetyl-beta-D-glucosaminidase the more significant differences concerned the isoenzyme I2-P (pregnancy). The pattern of the lysosomal enzymes in the twins resembled that of neonates of diabetic mothers who had had no insulin therapy. Since lysosomal enzymes are considered to be particularly sensitive indicators of carbohydrate metabolism abnormalities, we conclude that twin pregnancies are more at risk for these abnormalities than single ones.
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PMID:Enzymes of lysosomal origin in plasma of twin neonates. 845 79

In patients suffering from insulin-dependent diabetes mellitus (IDDM) with or without preclinical and clinical signs of diabetic nephropathy, the degree of epithelial cell lesions in the renal tubules was assessed from the urinary activities of enzymes at various sites, such as lysosomal (N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (beta-GA)), brush edge membranous (alanine aminopeptidase (AAP), and cytosolic (alpha-glucosidase (alpha-GL)). Patients from Groups 1 and 2 had no preclinical and clinical signs of nephropathy. In Group 1 patients, the magnitude of enzymuria was not different from that in normalcy. However, Group 2 patients exhibited significant increases in urinary NAG and beta-GA activities as compared to Group 1 patients and healthy individuals. In Group 3 patients with microproteinuria from 0.05 to 0.5 mg protein per ml urine, displayed a further enhancement of NAG and beta-GA activities as compared to Group 2 patients and significantly higher activity than did Groups 1 and 2 patients and healthy individuals. In Group 4 patients with macroproteinuria of > 0.5 mg/ml), greater increases in the activities of NAG, beta-GA, and AAP were not found, however, there was a significant increase in alpha-G1 activity. The findings suggest the varying degrees of epithelial cell damage in the renal tubules in patients of different groups and the possibility of early detection of lesion in the proximal portion of nephronic tubules in IDDM patients as assessed from urinary enzyme levels.
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PMID:[Urinary enzymes in insulin-dependent diabetes mellitus]. 899 62

This paper reports the active glycosidases in normal human lenses and their partial properties. In addition, variations in their enzyme activities during aging and with the advance of lens coloration were also examined. Five glycosidases, alpha-glucosidase, beta-D-glucuronidase, N-acetyl-beta-D-glucosaminidase, beta-D-cellobiosidase, and alpha-L-fucosidase, were detected as active glycosidases in the normal human lens. However, the activity of beta-D-cellobiosidase was considerably low as compared to the other four glycosidases. Thus, this enzyme was omitted from this study. The four glycosidases, alpha-D-glucosidase, beta-D-glucuronidase, N-acetyl-beta-D-glucosaminidase, and alpha-L-fucosidase, showed that their enzyme activities fell abruptly between the ages of 40 and 50. Furthermore, the Km values of their enzymes exhibited some variability during aging. Namely, the Km values of their enzymes indicated the lowest value between the 40 age group and 50 age group, suggesting that the substrate affinity became the strongest at these age groups. Then, variations in enzyme activity with the advance of lens coloration were examined. In each cases, the specific activity of detectable glycosidases in color lenses, white to brown, decreased. In particular, the specific activity of enzymes in the brown lens was very low, indicating that glycosidases in the brown lens may scarcely display their enzyme activities.
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PMID:Partial properties of four glycosidases in normal human lens and variations in their enzyme activities during aging and with the advance of lens coloration. 978 52

Some lysosomal glycohydrolases (N-acetyl-beta-D-glucosaminidase and their major isoenzymes, beta-D-glucuronidase, alpha-D-galactosidase, beta-D-galactosidase and alpha-D-glucosidase) were investigated in the plasma of 36 preterm infants with respiratory distress, 11 of whom developed bronchopulmonary dysplasia (BPD), in order to evaluate the role of the lysosomal apparatus in the disease. Enzyme activity was assayed fluorimetrically; the major N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes were separated using a routine chromatofocusing procedure; the diagnostic efficiency was evaluated by Bayes theorem. The mean levels of almost all glycohydrolases considered were significantly higher in BPD than in non-BPD infants. Among NAG major isoenzymes, an increase was found only in form A. No variation was evident in the plasma levels of glycohydrolases during dexamethasone therapy. Data from a retrospective analysis performed in all preterms considered, show that alpha-D-galactosidase and beta-D-galactosidase differentiate a posteriori BPD and non-BPD subjects. These enzymes, after a priori verification of their diagnostic potential in preterm infants at risk of BPD development, could acquire an important predictive value.
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PMID:Lysosomal enzymes in preterm infants with bronchopulmonary dysplasia: a potential diagnostic marker. 987 21

Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g.. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e.. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
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PMID:Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat. 1038 96

The erythrocyte membrane in 71 patients with type 2 diabetes mellitus was assessed for glycohydrolase activity: N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha- and beta-D-galactosidase, alpha- and beta-D-glucosidase, alpha-D-mannosidase, and alpha-L-fucosidase. Only beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase showed markedly elevated levels with respect to the controls regardless of the presence of complications. Among the examined patients, those with good metabolic control (not yet submitted to any therapy) showed the same enzyme levels as the reference subjects, while the levels in patients with unsatisfactory metabolic control (treated with oral hypoglycemic and/or insulin) significantly differed from the control levels. For alpha-D-glucosidase and beta-glucosidase, a correlation with glycemia and the parameters of metabolic control was also evidenced. Alterations of beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase were also ascertained in the plasma of the same diabetic patients according to the literature; each enzyme correlated with the other, either in plasma or in the erythrocyte membrane. This study shows a correlation between plasma and erythrocyte membrane levels for these three enzymes. The strict parallelism of the glycohydrolases in the two different compartments provides a profile of these enzymes in the pathology of diabetes.
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PMID:Alterations in the activity of several glycohydrolases in red blood cell membrane from type 2 diabetes mellitus patients. 1042 Dec 18


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