Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripherally active anorectic agents represent a new approach to the pharmacological management of obesity. Two inhibitors of carbohydrate absorption: an alpha-glucosidase inhibitor, acarbose (Bay g 5421) and a alpha-amylase inhibitor, Ro 12-2272, were compared with two novel inhibitors of lipid metabolism: an inhibitor of human pancreatic lipase (Ro 20-0083) and of hepatic fatty acid synthesis (Ro 22-0654). All drugs were presented as diet admixtures over 3 or 4 consecutive days. Total food and water intakes, the temporal pattern of feeding, and the average meal frequency and meal size were measured using computerized data collection procedures. Inhibitors of carbohydrate absorption failed to suppress food intake in either obese or lean Zucker rats and had no effect on the parameters of feeding. In contrast, inhibitors of lipid metabolism reduced food intake by 56-77% by reducing both meal frequency and meal size. Direct inhibition of lipid metabolism may be a viable mechanism for anti-obesity agents.
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PMID:Effects of inhibitors of carbohydrate absorption or lipid metabolism on meal patterns of Zucker rats. 384 Dec 13

The screening for enzyme inhibitors of microbial origin in the past decades has been a prosperous area to find new metabolites that are of potential importance as therapeutic or antibiotic agents. This review attempts a survey of recent achievements in this type of screening. Special emphasis is given to enzyme inhibitors and screening systems in fields where industry has a main interest in development. This includes some notes on the improved methodology for the detection of reversible and irreversible inhibitors of beta-lactamases and the presentation of a unique inhibitor of alpha-amylase from porcine pancreas isolated from a strain of Streptomyces tendae. This inhibitor (HOE 467) may be of potential use in the treatment of diabetic conditions, obesity and adipositas. The results show that the screening for enzyme inhibitors from microorganisms still provides one of the central challenges for future research.
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PMID:Enzyme inhibitors of microbial origin. 615 62

A rapid method is proposed for isolating the two main components of human pancreatic alpha-amylase (HPA I and HPA II). The isoelectric point of HPA I (7.2), the main component, was determined using an isoelectrofocusing method and found to differ from that of HPA II (6. 6). The molecular mass of HPA I (55862+/-5 Da) and that of HPA II (55786+/-5 Da) were determined by performing mass spectrometry and found to be quite similar to that of the protein moiety calculated from the amino acid sequence (55788 Da), which indicates that the human amylase is not glycosylated. The structure of both HPA I and HPA II was further investigated by performing limited proteolysis. Two fragments with an apparent molecular mass of 41 kDa and 14 kDa were obtained by digesting the isoforms with proteinase K and subtilisin, whereas digestion with papain yielded two cleaved fragments with molecular masses of 38 kDa and 17 kDa. Proteinase K and subtilisin susceptible bonds are located in the L8 loop (A domain), while the papain cut which occurs in the presence of the calcium chelator EDTA is in the L3 loop (B domain). The kinetics of the inhibition of HPA I and HPA II by acarbose, a drug used to treat diabetes and obesity, were studied using an amylose substrate. The Lineweaver-Burk primary plots of HPA I and HPA II, which did not differ significantly, indicated that the inhibition was of the mixed non-competitive type. The secondary plots gave parabolic curves. All in all, these data provide evidence that two acarbose molecules bind to HPA. In conclusion, apart from the pI, no significant differences were observed between HPA I and HPA II as regards either their molecular mass and limited proteolysis or their kinetic behavior. As was to be expected in view of the high degree of structural identity previously found to exist between human and porcine pancreatic amylases, the present data show that the inhibitory effects of acarbose on the kinetic behavior of these two amylases are quite comparable. In particular, the process of amylose hydrolysis catalyzed by HPA as well as by PPA in both cases requires two carbohydrate binding sites in addition to the catalytic site.
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PMID:The human pancreatic alpha-amylase isoforms: isolation, structural studies and kinetics of inhibition by acarbose. 977 2

The ability to control carbohydrate digestion is useful in the treatment of diabetes mellitus and obesity. In the present study, we examined whether recently developed 4(2)-O-beta-D-galactosyl maltobionolactone (LG2O) having anti-amylase activity is able to control postprandial blood glucose concentration in mice. In addition, we tried to determine how LG2O regulates carbohydrate delivery in the gut lumen by conducting in vivo and in vitro studies. Male non-diabetic ddY mice and KK-A(y) mice, a spontaneously diabetic strain, had free access to a carbohydrate rich diet supplemented with LG2O (3 or 10 g/kg) for 0.5 hr, and blood glucose concentration was measured. LG2O suppressed any steep increase in postprandial blood glucose concentration in both ddY and KK-A(y) mice. Corresponding to the blood glucose response, LG2O also markedly suppressed any increase in postprandial plasma insulin concentration. After ingestion of the diet, LG2O produced a 1.5-3.5 fold increase in the gut contents and reducible sugar content in the small intestine but not in the stomach. Although alpha-amylase activity in the stomach was much lower compared with the activity in the small intestine, LG2O still strongly inhibited alpha-amylase activity in the stomach. In contrast, LG2O had little or no influence on alpha-amylase activity in the proximal intestine. From the in vitro carbohydrate digestion stimulation, LG2O at 7.5 mM decreased glucose production by 75% for dextrin, 25% for alpha-starch and 60% for raw starch. In conclusion, administration of LG2O inhibits carbohydrate digestion in the gut, and produces significant improvements in both blood glucose and insulin response following ingestion as part of the diet, and this evidence provides support for its therapeutic potential in treating diabetes mellitus and obesity.
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PMID:Control of postprandial hyperglycaemia by galactosyl maltobionolactone and its novel anti-amylase effect in mice. 1212 61

In preliminary experiments, polyphenol fractions prepared from the leaves of Salix matsudana reduced the elevation of the rat plasma triacylglycerol level at 3 and 4 h after oral administration of a lipid emulsion containing corn oil, at a dose of 570 mg/kg. The present study examined the anti-obesity action of polyphenol fractions of S. matsudana leaves by testing whether the polyphenol fractions prevented the obesity induced by feeding a high-fat diet to female mice for 9 weeks. Body weights at 2-9 weeks and the fi nal parametrial adipose tissue weights were significantly lower in mice fed the high-fat diet with 5% polyphenols of S. matsudana leaves than in those fed the high-fat diet alone. The polyphenols of S. matsudana leaves also significantly reduced the hepatic total cholesterol content, which was elevated in mice fed the high-fat diet alone. In addition, the polyphenol fractions of S. matsudana leaves inhibited palmitic acid uptake into brush border membrane vesicles prepared from rat jejunum and alpha-amylase activity, and their fractions enhanced norepinephrine-induced lipolysis in fat cells. In conclusion, it is suggested that the inhibitory effects of the flavonoid glycoside fraction of S. matsudana leaves on high-fat diet-induced obesity might be due to the inhibition of carbohydrate and lipid absorption from small intestine through the inhibition of alpha-amylase and palmitic acid uptake into small intestinal brush border membrane or by accelerating fat mobilization through enhancing norepinephrine-induced lipolysis in fat cells.
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PMID:Anti-obesity action of Salix matsudana leaves (Part 1). Anti-obesity action by polyphenols of Salix matsudana in high fat-diet treated rodent animals. 1466 54

The inhibitory effect of 0.19 alpha-amylase inhibitor (0.19 AI) from wheat kernel on the porcine pancreas alpha-amylase (PPA)-catalyzed hydrolysis of p-nitrophenyl-alpha-D-maltoside (pNP-G2) was examined. 0.19 AI is a homodimer of 26.6 kDa with 13.3-kDa subunits under the conditions used. The elution behaviors in gel filtration HPLC of PPA and 0.19 AI indicated that a PPA molecule bound with a 0.19 AI molecule (homodimer) at a molar ratio of 1:1. 0.19 AI inhibited PPA activity in a competitive manner with an inhibitor constant, K(i), of 57.3 nM at pH 6.9, 30 degrees C, and the binding between them was found to be endothermic and entropy-driven. The activation energy for the thermal inactivation of 0.19 AI was determined to be 87.0 kJ/mol, and the temperature, T(50), giving 50% inactivation in a 30-min incubation at pH 6.9 was 88.1 degrees C. The high inhibitory activity of 0.19 AI against PPA and its high thermal stability suggest its potential for use in the prevention and therapy of obesity and diabetes.
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PMID:Inhibitory effect of 0.19 alpha-amylase inhibitor from wheat kernel on the activity of porcine pancreas alpha-amylase and its thermal stability. 1511 41

The leaf of Nelumbo nucifera Gaertn. (family Nymphaeaceae) has been used for summer heat syndrome as home remedy in Japan and China, and it has recently been used to treat obesity in China. So we investigate the pharmacological mechanism of the anti-obesity effect of Nelumbo nucifera leaves extract (NNE). We examined the effect of NNE on digestive enzyme activity, lipid metabolism and theromogenesis and evaluated the effects of anti-obesity using high-fat diet-induced obesity in mice that were treated with NNE for 5 weeks. NNE caused a concentration-dependent inhibition of the activities of alpha-amylase and lipase, and up-regulated lipid metabolism and expression of UCP3 mRNA in C2C12 myotubes. NNE prevented the increase in body weight, parametrial adipose tissue weight and liver triacylglycerol levels in mice with obesity induced by a high-fat diet. UCP3 mRNA expression in skeletal muscle tended to be higher, when mice were administrated by NNE and were exercised. Therefore, NNE impaired digestion, inhibited absorption of lipids and carbohydrates, accelerated lipid metabolism and up-regulated energy expenditure. Consequently, NNE is beneficial for the suppression of obesity.
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PMID:Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. 1649 25

The evidence for the effect of polyphenol components of berries on digestive enzymes is reviewed. Anthocyanins inhibit alpha-glucosidase activity and can reduce blood glucose levels after starch-rich meals, a proven clinical therapy for controlling type II diabetes. Ellagitannins inhibit alpha-amylase activity and there is potential for synergistic effects on starch degradation after ingestion of berries such as raspberries and strawberries, which contain substantial amounts of ellagitannins and anthocyanins. A range of berry polyphenols (e.g. flavonols, anthocyanidins, ellagitannins and proanthocyanidins) can inhibit protease activities at levels which could affect protein digestion in the gastrointestinal tract. In contrast, potential for the inhibition of gastrointestinal lipase activity, a proven therapeutic target for the control of obesity through reduced fat digestion, may be limited to proanthocyanidins. Taking into account the manifold possible synergies for inhibition of starch, protein and/or lipid digestion by the spectrum of polyphenol components present within berry species, the inhibition of digestive enzymes by dietary polyphenols may represent an under-reported mechanism for delivering some of the health benefits attributed to a diet rich in fruit and vegetables.
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PMID:The inhibitory effects of berry polyphenols on digestive enzymes. 1649 5

The hypoglycaemic efficacy of sumac (Rhus coriaria L.) and black cumin (Bunium persicum Boiss) extracts were investigated through inhibition of a glycoside hydrolase: alpha-amylase. On the basis of our result ethyl acetate extract of sumac may have interest in the treatment and prevention of hyperglycaemia, diabetes and obesity, with an IC50 value of 28.7 microg mL-1.
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PMID:Hypoglycaemic activity of two spices extracts: Rhus coriaria L. and Bunium persicum Boiss. 1675 27

Specific inhibitors of human pancreatic alpha-amylase (HPA) have potential as oral agents for the control of blood glucose levels in the treatment of diabetes and obesity. In a search for novel inhibitors, a library of 30 000 crude biological extracts of terrestrial and marine origin has been screened. A number of inhibitory extracts were identified, of which the most potent was subjected to bioassay-guided purification. A family of three glycosylated acyl flavonols, montbretins A-C, was thereby identified and characterized as competitive amylase inhibitors, with K(i) values ranging from 8.1-6100 nM. Competitive inhibition by myricetin, which corresponds to the flavone core, and noncompetitive inhibition by a second fragment, ethyl caffeiate, suggest a binding mode for these inhibitors.
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PMID:The search for novel human pancreatic alpha-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts. 1821 74


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