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 one of the most prevalant diseases of adults. Agents with alpha-glucosidase inhibitory activity have been useful as oral hypoglycemic drugs for the control of hyperglycemia in patients with type 2; noninsulin-dependent, diabetes mellitus (NIDDM). Investigation of some medicinal herbs: Urtica dioica, Taraxacum officinale, Viscum album, and Myrtus communis with alpha-glucosidase inhibitor activity was conducted to identify a prophylactic effect for diabetes in vitro. All plants showed differing potent alpha-glucosidase inhibitory activity. However, Myrtus communis strongly inhibited the enzyme (IC50 = 38 microg/mL). The inhibitory effect of these plants and some common antidiabetic drugs against the enzyme source (baker's yeast, rabbit liver, and small intestine) were also searched. Approximately all inhibitors used in this study showed quite different inhibitory activities, according to alpha-glucosidase origins. Furthermore, subsequent separation of the active material from Myrtus communis by HPLC showed that only one fraction acted as an a-glucosidase inhibitor.
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PMID:Inhibition of alpha-glucosidase by aqueous extracts of some potent antidiabetic medicinal herbs. 1570 95

Long-term type 2 diabetes can lead to numerous biological complications, such as hypertension and cardio-vascular disease. Key enzymes involved in the enzymatic breakdown of complex carbohydrates,pancreatic alpha-amylase and intestinal alpha-glucosidase, have been targeted as potential avenues for modulation of type 2 diabetes-associated post-prandial hyperglycemia through mild inhibition of their enzymatic activities so as to decrease meal-derived glucose absorption. Further, inhibition of hypertension-linked angiotensin I-converting enzyme (ACE) was targeted as a potential approach for modulation of diabetes-linked hypertension. Water-soluble extracts of soybean optimized for phenolic content via sprouting or bioprocessing by dietary fungus (Rhizopus oligosporus, Lentinus edodes) were investigated for inhibitory activity against porcine pancreatic alpha-amylase (PPA), yeast alpha-glucosidase, and rabbit lung ACE in vitro. PPA was allowed to react with each phenolic-optimized extract and the derivatized enzyme-phytochemical mixtures obtained were characterized for residual amylase activity. Alpha-glucosidase and ACE activities were determined in the presence of each phenolic-optimized extract. All of the soybean extracts possessed marked anti-amylase activity, with extracts of R. oligosporus-bioprocessed soybean having the strongest inhibitory activity, but only slight anti-glucosidase activity. The anti-amylase activity of each extract seemed associated with extract antioxidant activity. Anti-enzyme activity was slightly associated with total soluble phenolic content per se, but seemed more associated to the length of sprouting or bioprocessing of the soybean substrate. Short-term sprouting or bioprocessing seemed to improve anti-amylase activity, while long-term sprouting or bioprocessing seemed to aid anti-glucosidase activity. While ACE activity was strongly inhibited by all of the soybean extracts (44-97%), only sprouting was found to increase this inhibition and bioprocessing of soybean with L. edodes decreased inhibitory activity of soybean extract. The results suggest that sprouting and dietary fungal bioprocessing of soybean improve the anti-diabetic potential of soybean extracts, potentially through modulation of the phenolic profile of the extract, and further suggest that enzyme inhibitory activity may be linked to phenolic antioxidant mobilization during spouting and/ or bioprocessing. The significance of food-grade, plant-based enzyme inhibitors for modulation of carbohydrate breakdown and control of glycemic index of foods in the context of preventing hyperglycemia and diabetes mellitus complications such as hypertension in the long-term is hypothesized and discussed.
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PMID:Anti-diabetic and anti-hypertensive potential of sprouted and solid-state bioprocessed soybean. 1592 31

The synthesis of analogues of the naturally occurring glycosidase inhibitor, salacinol, in which the D-arabinitol ring has been replaced by D-lyxitol or D-ribitol, is described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata, which are traditionally used in India and Sri Lanka for the treatment of Type II diabetes. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-lyxitol or 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-ribitol at the least hindered carbon of the benzylidene-protected L-cyclic sulfate derived from L-erythritol. Screening of these compounds against recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligosaccharides of glucose into glucose itself, shows that they are not effective inhibitors of MGA and demonstrates the importance of the d-arabinitol configuration in the heterocyclic ring for effective inhibition.
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PMID:Synthesis of D-lyxitol and D-ribitol analogues of the naturally occurring glycosidase inhibitor salacinol. 1619 22

Impaired glucose metabolism is associated with an increased risk of cardiovascular events and cardiovascular-associated mortality. Postprandial hyperglycaemia is one of the earliest identifiable indicators of impaired glucose control. It contributes to the progression from impaired glucose tolerance to overt type 2 diabetes and exacerbates chronic hyperglycaemia in established diabetes. It is also an independent risk factor for cardiovascular disease in patients with impaired glucose tolerance and type 2 diabetes. Thus, an important strategy to reduce cardiovascular risk in patients with impaired glucose metabolism is to reduce postprandial glucose excursions. Acarbose, an alpha (alpha)-glucosidase inhibitor, reduces postprandial hyperglycaemia by delaying carbohydrate absorption from the small intestine. This mechanism of action provides glycaemic control without increasing insulin levels and exacerbating coexisting cardiovascular risk factors. The Study to Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) assessed the ability of acarbose to reduce cardiovascular risk. In this study of 1429 individuals with impaired glucose tolerance, acarbose therapy reduced the risk of any cardiovascular event by 49% (P=0.03), of an acute myocardial infarction by 91% (P=0.02) and of developing hypertension by 34% (P=0.006). Furthermore, a retrospective meta-analysis of randomised studies of acarbose in type 2 diabetes patients showed that acarbose therapy reduced the risk of any cardiovascular event by 35% (P=0.006) and the risk of a myocardial infarction by 64% (P=0.012). These results suggest that acarbose is useful in reducing the risk of cardiovascular events in patients with impaired glucose metabolism.
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PMID:Cardiovascular benefits of acarbose in impaired glucose tolerance and type 2 diabetes. 1633 93

Four chain extended homologues of salacinol, a naturally occurring glycosidase inhibitor, were prepared for evaluation as inhibitors of glucosidase enzymes involved in the breakdown of carbohydrates. The syntheses involved the reactions of 1,4-anhydro-2,3,5-tri-O-benzyl-4-thio-D-arabinitol with cyclic sulfate derivatives of different monosaccharides. Debenzylation of the products afforded the novel sulfonium sulfate derivatives of D-glucose, D-galactose, D-arabinose, and D-xylose that are of interest in their own right as glycosidase inhibitors. Reduction to the corresponding alditols then afforded the homologues of salacinol containing polyhydroxylated, acyclic chains of 5- and 6-carbons, differing in stereochemistry at the stereogenic centers. Three of the chain-extended homologues inhibited recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with Ki values in the low micromolar range, of approximately the same magnitude as salacinol, thus providing lead candidates for the treatment of Type 2 diabetes.
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PMID:Synthesis of sulfonium sulfate analogues of disaccharides and their conversion to chain-extended homologues of salacinol: new glycosidase inhibitors. 1643 29

Water soluble cranberry-based phytochemical combinations with oregano, rosemary, and Rhodiola rosea were evaluated for total phenolic content, related antioxidant activity and inhibition of diabetes management-related alpha -glucosidase, pancreatic alpha-amylase inhibition, and hypertension-related ACE-I inhibitory activities. Water extracts of oregano had 114.9 mg/g DW of phenolics which was highest among all the extracts tested, whereas the 75% cranberry with 25% oregano combinations had the highest phenolics (38.9 mg/g DW) among all the combinations tested. The water extracts of oregano had the highest DPPH radical inhibition activity (73.6 %), whereas among combinations the 75% cranberry and 25% oregano had the highest DPPH radical inhibition activity (50.8 %). These results indicated a correlation between total phenolic content and antioxidant activity. The water extracts of pure Rhodiola rosea had the highest alpha -glucosidase inhibition, whereas the 75% cranberry and 25% Rhodiola rosea combination had the highest inhibition among the combinations. In the case of alpha -amylase inhibition the water extracts of Rhodiola rosea had the highest inhibition, whereas the 75% cranberry with 25% Rhodiola rosea combination had the highest inhibition among the combinations. All the water extracts tested indicated that they had anti-ACE-I inhibitory activity. More specifically, among the water extracts 100% cranberry had the highest ACE-I inhibitory activity and among the combination the 75% cranberry with 25% rosemary had the highest ACE-I inhibitory activity. The analysis of alpha -glucosidase,alpha -amylase, and ACE-I inhibitory activities suggested that inhibition depend on the phenolic profile of each unique extract and by bringing together synergistic combinations to cranberry, health beneficial functionality was enhanced. This enhanced functionality in terms of high alpha -glucosidase and alpha -amylase inhibitory activities indicate the potential for diabetes management, and high ACE-I inhibitory activity indicates the potential for hypertension management.
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PMID:Potential of cranberry-based herbal synergies for diabetes and hypertension management. 1683 38

Type 2 diabetes mellitus in children and adolescents is becoming an increasingly important public health concern throughout the world. This epidemic is closely associated with the increased prevalence of obesity among youth of all ethnic backgrounds, as increased visceral adipose tissue produces adipokines that increase insulin resistance. Type 2 diabetes represents one arm of the metabolic syndrome, which includes abdominal obesity, disturbed glucose regulation and insulin resistance, dyslipidemia, and hypertension. The treatment of type 2 diabetes and the metabolic syndrome poses a challenge for pediatric endocrinologists. This review provides information regarding diagnosis of type 2 diabetes in children, as well as prevention strategies, such as lifestyle modification and pharmacologic options for weight loss, including metformin, orlistat, and sibutramine. Pharmacologic treatment options, their modes of action, and clinical indications for use are also reviewed. Treatment regimens for youth-onset type 2 diabetes that are discussed include metformin, sulfonylureas, glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1, and insulin.
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PMID:The treatment of type 2 diabetes mellitus in youth : which therapies? 1687 99

The increased risk of cardiovascular disease associated with type 2 diabetes is well documented. Lesser degrees of abnormal glucose metabolism including impaired fasting glycaemia and impaired glucose tolerance are also associated with increased cardiovascular risk. Studies showing improved cardiovascular outcomes with oral antidiabetic agents are limited, with the UKPDS demonstrating improved macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes treated with metformin, and the heavily criticized STOP NIDDM trial showing a reduction in the number of cardiovascular events with the alpha glucosidase inhibitor acarbose. In recent years there has been an increase in the number of oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some of these drugs have complex metabolic properties, additional to their antihyperglycaemic effect, improving endothelial function and markers of atherogenesis, with the potential to reduce cardiovascular morbidity and mortality, as supported by the recently published results of the PROACTIVE study. The results of further long-term cardiovascular outcome studies with these newer agents are awaited.
Diabetes Obes Metab 2007 Jan
PMID:Oral antidiabetic agents as cardiovascular drugs. 1719 15

Mulberry 1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor, has been hypothesized to be beneficial for the suppression of abnormally high blood glucose levels and thereby prevention of diabetes mellitus. However, DNJ contents in commercial mulberry products were as low as about 0.1% (100 mg/100 g of dry product), implying that the bioavailability of DNJ might not be expected. We carried out studies in two directions: (1) production of food-grade mulberry powder containing a maximally high DNJ content; (2) determination of the optimal dose of the DNJ-enriched powder for the suppression of the postprandial blood glucose through clinical trials. The following method was used: (1) DNJ concentrations in mulberry leaves from different cultivars, harvest seasons, and leaf locations were determined using hydrophilic interaction chromatography with evaporative light scattering detection. (2) Healthy volunteers received 0, 0.4, 0.8, and 1.2 g of DNJ-enriched powder (corresponding to 0, 6, 12, and 18 mg of DNJ, respectively), followed by 50 g of sucrose. Before and 30-180 min after the DNJ/sucrose administration, plasma glucose and insulin were determined. The following results were obtained: (1) Young mulberry leaves taken from the top part of the branches in summer contained the highest amount of DNJ. After optimization of the harvesting and drying processes for young mulberry leaves (Morus alba L. var. Shin ichinose), DNJ-enriched powder (1.5%) was produced. (2) A human study indicated that the single oral administration of 0.8 and 1.2 g of DNJ-enriched powder significantly suppressed the elevation of postprandial blood glucose and secretion of insulin, revealing the physiological impact of mulberry DNJ (effective dose and efficacy in humans). This study suggests that the newly developed DNJ-enriched powder can be used as a dietary supplement for preventing diabetes mellitus.
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PMID:Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans. 1755 27

1-deoxynojirimycin (DNJ), a potent glucosidase inhibitor, is a characteristic constituent of the mulberry leaf. Dietary mulberry DNJ may be beneficial for the suppression of abnormally high blood glucose levels, thereby preventing diabetes mellitus. Although there is considerable interest in the effects of mulberry DNJ, the intestinal absorption and pharmacokinetic profile of orally administered mulberry DNJ have never been characterized. In this study, we developed a method for determining the level of plasma DNJ by hydrophilic interaction chromatography coupled to a mass spectrometric detector (HILIC-MS) to investigate the absorption and metabolism of orally administered mulberry DNJ in rats. DNJ was separated from plasma extract on a TSK gel Amide-80 column, a representative column for HILIC. At postcolumn, DNJ was concurrently detected and identified by MS. The plasma DNJ concentration in fasted rats was below the detection limit [<1 microg (6 nmol)/mL]; however, the concentration reached a maximum [15 microg (92 nmol)/mL] 30 min after the administration of mulberry DNJ (110 mg/kg of body weight), and the DNJ concentration decreased rapidly thereafter. When the rats received different amounts of mulberry DNJ (1.1, 11, and 110 mg/kg of body weight), dose-dependent incorporation of DNJ into the plasma was confirmed. We did not detect any DNJ metabolites in the plasma. These findings indicate that orally administered mulberry DNJ is absorbed as an intact form from the alimentary tract and then is quickly excreted from the body. The developed HILIC-MS method could be applied in determining levels of DNJ in urine and tissues, and therefore, the method would be a powerful tool for studying the metabolic fate of mulberry DNJ as well as its bioavailability.
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PMID:Occurrence of orally administered mulberry 1-deoxynojirimycin in rat plasma. 1791 70


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