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 phosphorylated form of liver glycogen phosphorylase (alpha-1,4-glucan : orthophosphate alpha-glucosyl-transferase, EC 2.4.1.1) (phosphorylase a) is active and easily measured while the dephosphorylated form (phosphorylase b), in contrast to the muscle enzyme, has been reported to be essentially inactive even in the presence of AMP. We have purified both forms of phosphorylase from rat liver and studied the characteristics of each. Phosphorylase b activity can be measured with our assay conditions. The phosphorylase b we obtained was stimulated by high concentrations of sulfate, and was a substrate for muscle phosphorylase kinase whereas phosphorylase a was inhibited by sulfate, and was a substrate for liver phosphorylase phosphatase. Substrate binding to phosphorylase b was poor (KM glycogen = 2.5 mM, glucose-1-P = 250 mM) compared to phosphorylase a (KM glycogen = 1.8 mM, KM glucose-1-P = 0.7 mM). Liver phosphorylase b was active in the absence of AMP. However, AMP lowered the KM for glucose-1-P to 80 mM for purified phosphorylase b and to 60 mM for the enzyme in crude extract (Ka = 0.5 mM). Using appropriate substrate, buffer and AMP concentrations, assay conditions have been developed which allow determination of phosphorylase a and 90% of the phosphorylase b activity in liver extracts. Interconversion of the two forms can be demonstrated in vivo (under acute stimulation) and in vitro with little change in total activity. A decrease in total phosphorylase activity has been observed after prolonged starvation and in diabetes.
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PMID:Characteristics of the dephosphorylated form of phosphorylase purified from rat liver and measurement of its activity in crude liver preparations. 0 75

The preventive effect of an immunopotentiator, beta-1,6;1,3 D-glucan, on the development of diabetes and insulitis was studied in BB rats. The intravenous administration of 1 mg kg-1 week-1 of beta-1,6;1,3 D-glucan from the age of 4 weeks decreased the cumulative incidence of diabetes from 43.3% (13/30) to 6.7% (2/30) (P less than 0.005) and also the incidence of insulitis from 82.4% (14/17) to 26.3% (5/19) at the age of 20 weeks (P less than 0.002). Eight of nine rats were free from diabetes for 5 weeks after stopping beta-1,6;1,3 D-glucan at the age of 20 weeks. The total numbers of leukocytes in the peripheral blood and spleen of the rats were increased by beta-1,6;1,3 D-glucan treatment (P less than 0.05), whereas their T lymphocytes subsets were not changed. These data indicate that immunopotentiators could modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes in BB rats.
Diabetes Res Clin Pract 1992 Aug
PMID:An immunopotentiator of beta-1,6;1,3 D-glucan prevents diabetes and insulitis in BB rats. 142 50

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

The aim of the current study was to characterize the effects of isolated and native sources of beta-glucan, oat gum, and oat bran, respectively, when incorporated into a complete meal. Fasting control subjects and subjects with Type 2 diabetes were fed porridge meals containing either wheat farina, wheat farina plus oat gum or oat bran. Blood samples were collected for 3 h after the test meals and plasma glucose and insulin were measured. Oat bran and wheat farina plus oat gum meals reduced the postprandial plasma glucose excursions and insulin levels when compared with the control wheat farina meal in both control and Type 2 diabetic subjects. This study shows that both the native cell wall fibre of oat bran and isolated oat gum, when incorporated into a meal, act similarly by lowering postprandial plasma glucose and insulin levels. A diet rich in beta-glucan may therefore be of benefit in the regulation of postprandial plasma glucose levels in subjects with Type 2 diabetes.
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PMID:High beta-glucan oat bran and oat gum reduce postprandial blood glucose and insulin in subjects with and without type 2 diabetes. 803 32

Recent recommendations for the dietary management of diabetes mellitus state that diet needs to be individualized so that there is improved glucose and lipid control in the patient. In a majority of individuals with diabetes, this is best done with a diet that is low in fat and high in carbohydrate, particularly that of cereal origin. However, symptoms of hyper- and hypoglycemia must be averted. Most cereal products, however, tend to have a high glycemic index Cereals such as Prowashonupana barley or fractions of oat bran are particularly high in the soluble fiber beta-glucan, which when taken with a meal increases the viscosity of the meal bolus once it has reached the small intestine, where the absorption of nutrients occurs. This high viscosity delays absorption. A 50% reduction in glycemic peak can be achieved with a concentration of 10% beta-glucan in a cereal food. A significant lowering of plasma LDL cholesterol concentrations can also be anticipated with the daily consumption of > or = 3 g of beta-glucan. Diabetic individuals can benefit from diets that are high in beta-glucan, which, as a component of oats and barley, can be incorporated into breakfast cereals and other products.
Diabetes Care 1997 Nov
PMID:The role of viscous soluble fiber in the metabolic control of diabetes. A review with special emphasis on cereals rich in beta-glucan. 935 22

Hyperinsulinemia predicts the development of type 2 diabetes, and family studies suggest that insulin levels are regulated in part by genes. We conducted a genome-wide scan to detect genes influencing variation in fasting serum insulin concentrations in 391 nondiabetic individuals from 10 large multigenerational families. Approximately 380 microsatellite markers with an average spacing of 10 cM were genotyped in all study subjects. Insulin concentrations measured by radioimmunoassay were transformed by their natural logarithms before analysis. In multipoint analysis, peak evidence for linkage occurred on chromosome 3p approximately 109 cM from pter in the region of 3p14.2-p14.1. The multipoint logarithm of odds (LOD) score was 3.07, occurring in the region flanked by markers D3S1600 and D3S1285 (P value by simulation <0.0001). In a two-point analysis, LOD scores ranged from 0.75 to 2.52 for the nine markers typed in the region spanning 88-143 cM from pter. The fasting insulin resistance index was highly correlated with fasting insulin concentrations in this sample and also provided strong evidence for linkage to this region (LOD = 2.99). There was no evidence in our genome-wide scan for linkage of insulin levels to any other chromosome. These results provide evidence that a gene-influencing variation in insulin concentrations exists on chromosome 3p. Possible candidate genes in this region include GBE1 and ACOX2, which encode enzymes involved in glycogen and fatty acid metabolism, respectively.
Diabetes 2000 Mar
PMID:Linkage of serum insulin concentrations to chromosome 3p in Mexican Americans. 1086 77

A nutrition rich in fibre has a preventive effect against constipation, colon diverticulosis, carcinoma of the large bowel and stomach, type 2-diabetes, metabolic syndrome and cardiovascular disease. In case of constipation, diverticulosis and diabetes this effect solely depends on dietary fibre. Regarding carcinomas and cardiovascular diseases, so far unknown factors integrated in or associated with fibre-rich food may also contribute to the preventive effect. Therapy with dietary fibre is indicated for constipation, colon diverticulosis, diarrhea, diabetes, and hypercholesterinemia. The individual dietary fibres differ substance-specifically. Food-integrated dietary fibre such as whole-grain bread, vegetables and fruit have their place in prevention. Dietary fibre preparations such as wheat bran, flax seed or sugar-beet fibre are useful in the treatment of constipation, colon diverticulosis and adiposity. Oat bran is preferentially used in hypercholesterinemia. Purified dietary fibres such as cellulose, guar, psyllium, and beta-glucan have an anti-diabetic, all viscous fibres an anti-lipaemic effect. The therapeutic dosages of dietary fibre preparations are 20-40 g/day and of purified fibres substances 10-20 g/day respectively.
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PMID:[Dietary fibre: more than a matter of dietetics. II. Preventative and therapeutic uses]. 1547 Nov 77

Beta-glucans are soluble fibers with physiological functions, such as interference with absorption of sugars and reduction of serum lipid levels. The objective of the present study was to analyze the distribution of beta-glucans in different tissues of the African grass species Rhynchelytrum repens and also to evaluate their hypoglycemic activity. Leaf blades, sheaths, stems, and young leaves of R. repens were submitted to extraction with 4 M KOH. Analysis of the fractions revealed the presence of arabinose, glucose, xylose, and traces of rhamnose and galactose. The presence of beta-glucan in these fractions was confirmed by hydrolyzing the polymers with endo-beta-glucanase from Bacillus subtilis, followed by HPLC analysis of the characteristic oligosaccharides produced. The 4 M KOH fractions from different tissues were subjected to gel permeation chromatography on Sepharose 4B, with separation of polysaccharides with different degrees of polymerization, the highest molecular mass (above 2000 kDa) being found in young leaves. The molecular mass of the leaf blade polymers was similar (250 kDa) to that of maize coleoptile beta-glucan used for comparison. The 4 M KOH fraction injected into rats with streptozotocin-induced diabetes showed hypoglycemic activity, reducing blood sugar to normal levels for approximately 24 h. This performance was better than that obtained with pure beta-glucan from barley, which decreased blood sugar levels for about 4 h. These results suggest that the activity of beta-glucans from R. repens is responsible for the use of this plant extract as a hypoglycemic drug in folk medicine.
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PMID:Hypoglycemic activity of polysaccharide fractions containing beta-glucans from extracts of Rhynchelytrum repens (Willd.) C.E. Hubb., Poaceae. 1593 82

There is growing support for the protective role of soluble fibre in type II diabetes. Soluble fibre beta-glucan found in cereal products including oats and barley may be the active component. There is evidence of postprandial blunting of blood glucose and insulin responses to dietary carbohydrates when oat soluble fibre is supplemented into the diet but few trials have been carried out using natural barley or enriched barley beta-glucan products. The aim of this trial was to investigate the postprandial effect of a highly enriched barley beta -glucan product on blood glucose, insulin and lipids when given with a high-CHO food and a high-CHO drink. 18 lean, healthy men completed a 4 treatment intervention trial comprising (i) high-CHO(food control), (ii) high-CHO(food+fibre), (iii) high-CHO(drink control), (iv) high-CHO(drink+fibre) where a 10g dose of barley beta-glucan fibre supplement (Cerogen) containing 6.31g beta-glucan was added to food and drink controls. There was an increase of glucose and insulin following all 4 treatments. Addition of the beta -glucan supplement significantly blunted the glycaemic and insulinaemic responses on the food (p<0.05) but not drink (p>0.05) treatments when compared to controls. The high-CHO breakfasts decreased total, LDL- and HDL-cholesterol from baseline to 60 mins postprandially but there were no differential effects of beta-glucan treatment on circulating lipids. We conclude that a high dose barley beta-glucan supplement can improve glucose control when added to a high-CHO starchy food, probably due to increased gastro-intestinal viscosity, but not when added to a high-CHO beverage where rapid absorption combined with decreased beta-glucan concentration and viscosity may obviate this mechanism.
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PMID:Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves postprandial glycaemic response for meals but not beverages. 1721 76

Non-cellulosic beta-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. These beta-glucans consist of a backbone of glucose residues linked by beta-(1-->3)-glycosidic bonds, often with attached side-chain glucose residues joined by beta-(1-->6) linkages. The frequency of branching varies. The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes. Their mechanisms of action involve them being recognized as non-self molecules, so the immune system is stimulated by their presence. Several receptors have been identified, which include: dectin-1, located on macrophages, which mediates beta-glucan activation of phagocytosis and production of cytokines, a response co-ordinated by the toll-like receptor-2. Activated complement receptors on natural killer cells, neutrophils, and lymphocytes, may also be associated with tumour cytotoxicity. Two other receptors, scavenger and lactosylceramide, bind beta-glucans and mediate a series of signal pathways leading to immunological activation. Structurally different beta-glucans appear to have different affinities toward these receptors and thus generate markedly different host responses. However, the published data are not always easy to interpret as many of the earlier studies used crude beta-glucan preparations with, for the most part, unknown chemical structures. Careful choice of beta-glucan products is essential if their benefits are to be optimized, and a better understanding of how beta-glucans bind to receptors should enable more efficient use of their biological activities.
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PMID:Medicinal importance of fungal beta-(1-->3), (1-->6)-glucans. 1759 Mar 23


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