The Experts below are selected from a list of 12636 Experts worldwide ranked by ideXlab platform
Robert G Gilbert - One of the best experts on this subject based on the ideXlab platform.
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metformin and berberine suppress glycogenolysis by inhibiting glycogen phosphorylase and stabilizing the molecular structure of glycogen in db db mice
Carbohydrate Polymers, 2020Co-Authors: Kaiping Wang, Robert G Gilbert, Mitchell A Sullivan, Jing Zhou, Bin DengAbstract:Glycogen is a branched Glucose Polymer involved in sustaining blood Glucose homeostasis. Liver glycogen comprises α particles (up to 300 nm in diameter) made of joined β particles (∼20 nm in diameter). Glycogen α particles in a mouse model for diabetes are molecularly fragile, breaking down into smaller β particles more readily than in healthy mice. Glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen degradation, is overexpressed in diabetic mice. This study shows that Metformin and Berberine, two common drugs, two common drugs used to treat diabetes, are able to revert the liver glycogen of diabetic mice to the stable structure seen in non-diabetic mice. It is also shown that these drugs reduce the GP level via the cAMP/PKA signaling pathway in diabetic livers and decrease the affinity of GP with the glycogen of db/db mice. These effects of these drugs may slow down the degradation of liver glycogen and improve Glucose homeostasis.
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Proteomic Investigation of the Binding Agent between Liver Glycogen β Particles
2018Co-Authors: Xinle Tan, Bin Deng, Mitchell A Sullivan, Sharif S. Nada, Benjamin L. Schulz, Robert G GilbertAbstract:Glycogen is a highly branched Glucose Polymer which plays an important role in Glucose storage and the maintenance of blood sugar homeostasis. The dimeric protein glycogenin can self-glucosylate to act as a primer for glycogen synthesis, eventually resulting in small (∼20 nm diameter) glycogen β particles with a dimer of glycogenin at their core. In the liver, glycogen is also found in the form of α particles: large bound composites of many β particles. Here, we provide evidence using qualitative and quantitative proteomics and size-exclusion chromatography from healthy rat, mouse, and human liver glycogen that glycogenin is the binding agent linking β particles together into α particles
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parameterizing amylose chain length distributions for biosynthesis structure property relations
Analytical and Bioanalytical Chemistry, 2017Co-Authors: Sharif S. Nada, Robert G Gilbert, Wei ZouAbstract:Amylose, one of the components of starch, is a Glucose Polymer consisting largely of long, linear chains with a few long-chain branch points. The chain-length (molecular weight) distribution (CLD) of the component chains of amylose can provide information on amylose biosynthesis-structure-property relations, as has been done previously by fitting amylopectin CLDs to a model with physically meaningful parameters. Due to the presence of long chains, the CLD of amylose can currently best be obtained by size-exclusion chromatography, a technique that suffers from band-broadening effects which alter the observed distribution. The features of the multiple regions present in amylose chain-length distributions are also difficult to resolve, an issue that combines with band broadening to compound the difficulty of analysis and subsequent parameterization of the structural characteristics of amylose. A new method is presented to fit these distributions with biologically meaningful parameters in a way that accounts for band broadening. This is achieved by assuming that band broadening takes the form of a simple Gaussian over a relatively small region and that chain stoppage is a random process independent of the length of the substrate chain over the same region; these assumptions are relatively weak and expected to be frequently applicable. The method provides inbuilt consistency tests for its applicability to a given data set and, in cases where it is applicable, allows for the first nonempirical parameterization of amylose biosynthesis-structure-property relations from CLDs by using parameters directly linked to the activities of the enzymes responsible for chain growth and chain stoppage.
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the molecular structural features controlling stickiness in cooked rice a major palatability determinant
Scientific Reports, 2017Co-Authors: Sangeeta Prakash, Timothy Nicholson, Robert G Gilbert, Melissa A Fitzgerald, Hongyan LiAbstract:The stickiness of cooked rice is important for eating quality and consumer acceptance. The first molecular understanding of stickiness is obtained from leaching and molecular structural characteristics during cooking. Starch is a highly branched Glucose Polymer. We find (i) the molecular size of leached amylopectin is 30 times smaller than that of native amylopectin while (ii) that of leached amylose is 5 times smaller than that of native amylose, (iii) the chain-length distribution (CLD: the number of monomer units in a chain on the branched Polymer) of leached amylopectin is similar to native amylopectin while (iv) the CLD of leached amylose is much narrower than that of the native amylose, and (v) mainly amylopectin, not amylose, leaches out of the granule and rice kernel during cooking. Stickiness is found to increase with decreasing amylose content in the whole grain, and, in the leachate, with increasing total amount of amylopectin, the proportion of short amylopectin chains, and amylopectin molecular size. Molecular adhesion mechanisms are put forward to explain this result. This molecular structural mechanism provides a new tool for rice breeders to select cultivars with desirable palatability by quantifying the components and molecular structure of leached starch.
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molecular structure of human liver glycogen
PLOS ONE, 2016Co-Authors: Bin Deng, Robert G Gilbert, Mitchell A Sullivan, Prudence O Powell, Cheng ChenAbstract:Glycogen is a highly branched Glucose Polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.
Mitchell A Sullivan - One of the best experts on this subject based on the ideXlab platform.
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metformin and berberine suppress glycogenolysis by inhibiting glycogen phosphorylase and stabilizing the molecular structure of glycogen in db db mice
Carbohydrate Polymers, 2020Co-Authors: Kaiping Wang, Robert G Gilbert, Mitchell A Sullivan, Jing Zhou, Bin DengAbstract:Glycogen is a branched Glucose Polymer involved in sustaining blood Glucose homeostasis. Liver glycogen comprises α particles (up to 300 nm in diameter) made of joined β particles (∼20 nm in diameter). Glycogen α particles in a mouse model for diabetes are molecularly fragile, breaking down into smaller β particles more readily than in healthy mice. Glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen degradation, is overexpressed in diabetic mice. This study shows that Metformin and Berberine, two common drugs, two common drugs used to treat diabetes, are able to revert the liver glycogen of diabetic mice to the stable structure seen in non-diabetic mice. It is also shown that these drugs reduce the GP level via the cAMP/PKA signaling pathway in diabetic livers and decrease the affinity of GP with the glycogen of db/db mice. These effects of these drugs may slow down the degradation of liver glycogen and improve Glucose homeostasis.
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Proteomic Investigation of the Binding Agent between Liver Glycogen β Particles
2018Co-Authors: Xinle Tan, Bin Deng, Mitchell A Sullivan, Sharif S. Nada, Benjamin L. Schulz, Robert G GilbertAbstract:Glycogen is a highly branched Glucose Polymer which plays an important role in Glucose storage and the maintenance of blood sugar homeostasis. The dimeric protein glycogenin can self-glucosylate to act as a primer for glycogen synthesis, eventually resulting in small (∼20 nm diameter) glycogen β particles with a dimer of glycogenin at their core. In the liver, glycogen is also found in the form of α particles: large bound composites of many β particles. Here, we provide evidence using qualitative and quantitative proteomics and size-exclusion chromatography from healthy rat, mouse, and human liver glycogen that glycogenin is the binding agent linking β particles together into α particles
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molecular structure of human liver glycogen
PLOS ONE, 2016Co-Authors: Bin Deng, Robert G Gilbert, Mitchell A Sullivan, Prudence O Powell, Cheng ChenAbstract:Glycogen is a highly branched Glucose Polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.
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molecular structure of glycogen in diabetic liver
Glycoconjugate Journal, 2015Co-Authors: Bin Deng, Robert G Gilbert, Mitchell A Sullivan, Xinle Tan, Chengjun Zhu, B SchulzAbstract:Liver glycogen (involved in maintaining blood-sugar levels) is a hyperbranched Glucose Polymer containing β particles (diameter ~20 nm), which can form composite α particles (diameter ~50–300 nm), and includes a small but significant amount of bound protein. Size distributions of glycogen from livers of healthy and diabetic mice were examined using size-exclusion chromatography with two separate eluents: aqueous eluent and dimethylsulfoxide (DMSO) eluent. Morphologies were examined with transmission electron microscopy. Diabetic glycogen (DG) exhibited many α particles in the mild water-based solvent, but in DMSO, which breaks H bonds, these degraded to β particles; α particles however were always present in healthy glycogen (HG). This DG fragility shows the binding of β into α particles is different in HG and DG. The diabetic α particle fragility may be involved with the uncontrolled blood-sugar release symptomatic of diabetes: small β particles degrade more easily to Glucose than α particles. This has implications for diabetes management.
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improving size exclusion chromatography separation for glycogen
Journal of Chromatography A, 2014Co-Authors: Mitchell A Sullivan, Robert G Gilbert, Francisco Vilaplana, Torsten Witt, Prudence O Powell, E RouraAbstract:Glycogen is a hyperbranched Glucose Polymer comprised of glycogen β particles, which can also form much larger composite α particles. The recent discovery using size-exclusion chromatography (SEC) that fewer, smaller, α particles are found in diabetic-mouse liver compared to healthy mice highlights the need to achieve greater accuracy in the size separation methods used to analyze α and β particles. While past studies have used dimethyl sulfoxide as the SEC eluent to analyze the molecular size and structure of native glycogen, an aqueous eluent has not been rigorously tested and compared with dimethyl sulfoxide. The conditions for SEC of pig-liver glycogen, phytoglycogen and oyster glycogen were optimized by comparing two different eluents, aqueous 50 mM NH₄NO₃/0.02% NaN₃ and dimethyl sulfoxide/0.5% LiBr, run through different column materials and pore sizes at various flow rates. The aqueous system gave distinct size separation of α- and β-particle peaks, allowing for a more detailed and quantitative analysis and comparison between liver glycogen samples. This greater resolution has also revealed key differences between the structure of liver glycogen and phytoglycogen.
Bin Deng - One of the best experts on this subject based on the ideXlab platform.
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metformin and berberine suppress glycogenolysis by inhibiting glycogen phosphorylase and stabilizing the molecular structure of glycogen in db db mice
Carbohydrate Polymers, 2020Co-Authors: Kaiping Wang, Robert G Gilbert, Mitchell A Sullivan, Jing Zhou, Bin DengAbstract:Glycogen is a branched Glucose Polymer involved in sustaining blood Glucose homeostasis. Liver glycogen comprises α particles (up to 300 nm in diameter) made of joined β particles (∼20 nm in diameter). Glycogen α particles in a mouse model for diabetes are molecularly fragile, breaking down into smaller β particles more readily than in healthy mice. Glycogen phosphorylase (GP), a rate-limiting enzyme in glycogen degradation, is overexpressed in diabetic mice. This study shows that Metformin and Berberine, two common drugs, two common drugs used to treat diabetes, are able to revert the liver glycogen of diabetic mice to the stable structure seen in non-diabetic mice. It is also shown that these drugs reduce the GP level via the cAMP/PKA signaling pathway in diabetic livers and decrease the affinity of GP with the glycogen of db/db mice. These effects of these drugs may slow down the degradation of liver glycogen and improve Glucose homeostasis.
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Proteomic Investigation of the Binding Agent between Liver Glycogen β Particles
2018Co-Authors: Xinle Tan, Bin Deng, Mitchell A Sullivan, Sharif S. Nada, Benjamin L. Schulz, Robert G GilbertAbstract:Glycogen is a highly branched Glucose Polymer which plays an important role in Glucose storage and the maintenance of blood sugar homeostasis. The dimeric protein glycogenin can self-glucosylate to act as a primer for glycogen synthesis, eventually resulting in small (∼20 nm diameter) glycogen β particles with a dimer of glycogenin at their core. In the liver, glycogen is also found in the form of α particles: large bound composites of many β particles. Here, we provide evidence using qualitative and quantitative proteomics and size-exclusion chromatography from healthy rat, mouse, and human liver glycogen that glycogenin is the binding agent linking β particles together into α particles
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molecular structure of human liver glycogen
PLOS ONE, 2016Co-Authors: Bin Deng, Robert G Gilbert, Mitchell A Sullivan, Prudence O Powell, Cheng ChenAbstract:Glycogen is a highly branched Glucose Polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.
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molecular structure of glycogen in diabetic liver
Glycoconjugate Journal, 2015Co-Authors: Bin Deng, Robert G Gilbert, Mitchell A Sullivan, Xinle Tan, Chengjun Zhu, B SchulzAbstract:Liver glycogen (involved in maintaining blood-sugar levels) is a hyperbranched Glucose Polymer containing β particles (diameter ~20 nm), which can form composite α particles (diameter ~50–300 nm), and includes a small but significant amount of bound protein. Size distributions of glycogen from livers of healthy and diabetic mice were examined using size-exclusion chromatography with two separate eluents: aqueous eluent and dimethylsulfoxide (DMSO) eluent. Morphologies were examined with transmission electron microscopy. Diabetic glycogen (DG) exhibited many α particles in the mild water-based solvent, but in DMSO, which breaks H bonds, these degraded to β particles; α particles however were always present in healthy glycogen (HG). This DG fragility shows the binding of β into α particles is different in HG and DG. The diabetic α particle fragility may be involved with the uncontrolled blood-sugar release symptomatic of diabetes: small β particles degrade more easily to Glucose than α particles. This has implications for diabetes management.
Joan C Ferrer - One of the best experts on this subject based on the ideXlab platform.
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inhibitory properties of 1 4 dideoxy 1 4 imino d arabinitol dab derivatives acting on glycogen metabolising enzymes
Organic and Biomolecular Chemistry, 2016Co-Authors: Mireia Diazlobo, Alda Lisa Concia, Livia Gomez, Pere Clapes, Ignacio Fita, Joan J Guinovart, Joan C FerrerAbstract:Glycogen synthase (GS) and glycogen phosphorylase (GP) are the key enzymes that control, respectively, the synthesis and degradation of glycogen, a multi-branched Glucose Polymer that serves as a form of energy storage in bacteria, fungi and animals. An abnormal glycogen metabolism is associated with several human diseases. Thus, GS and GP constitute adequate pharmacological targets to modulate cellular glycogen levels by means of their selective inhibition. The compound 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) is a known potent inhibitor of GP. We studied the inhibitory effect of DAB, its enantiomer LAB, and 29 DAB derivatives on the activity of rat muscle glycogen phosphorylase (RMGP) and E. coli glycogen synthase (EcGS). The isoform 4 of sucrose synthase (SuSy4) from Solanum tuberosum L. was also included in the study for comparative purposes. Although these three enzymes possess highly conserved catalytic site architectures, the DAB derivatives analysed showed extremely diverse inhibitory potential. Subtle changes in the positions of crucial residues in their active sites are sufficient to discriminate among the structural differences of the tested inhibitors. For the two Leloir-type enzymes, EcGS and SuSy4, which use sugar nucleotides as donors, the inhibitory potency of the compounds analysed was synergistically enhanced by more than three orders of magnitude in the presence of ADP and UDP, respectively. Our results are consistent with a model in which these compounds bind to the subsite in the active centre of the enzymes that is normally occupied by the glucosyl residue which is transferred between donor and acceptor substrates. The ability to selectively inhibit the catalytic activity of the key enzymes of the glycogen metabolism may represent a new approach for the treatment of disorders of the glycogen metabolism.
Antonio Daniele Pinna - One of the best experts on this subject based on the ideXlab platform.
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p o p a study prevention of postoperative abdominal adhesions by icodextrin 4 solution after laparotomy for adhesive small bowel obstruction a prospective randomized controlled trial
Journal of Gastrointestinal Surgery, 2012Co-Authors: Fausto Catena, Luca Ansaloni, Salomone Di Saverio, Antonio Daniele PinnaAbstract:Background Adhesive small bowel obstruction (ASBO) is an important cause of hospital admission, is associated with significant morbidity and mortality, and therefore is a substantial burden for healthcare systems worldwide. Icodextrin 4% solution (Adept, Shire Pharmaceuticals, UK) is a high-molecular-weight a-1,4 Glucose Polymer approved in Europe for use as intraoperative lavage and postoperative instillation to reduce the occurrence of post-surgery intra-abdominal adhesions. The present clinical study aimed to evaluate the safety and effectiveness of icodextrin 4% in decreasing the incidence, extent, and severity of adhesions in patients after abdominal surgery for ASBO.
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prospective controlled randomized trial on prevention of postoperative abdominal adhesions by icodextrin 4 solution after laparotomic operation for small bowel obstruction caused by adherences popa study prevention of postoperative adhesions on behalf of the world society of emergency surgery
Trials, 2008Co-Authors: Fausto Catena, Luca Ansaloni, A Lauro, Giorgio Ercolani, Luigi Dalessandro, Antonio Daniele PinnaAbstract:Background Adhesive small intestine occlusion [ASIO] is an important cause of hospital admission placing a substantial burden on healthcare systems worldwide. Often times, ASIO is associated with significant morbidity and mortality. Icodextrin 4% solution [Adept, Shire Pharmaceuticals, UK] is a high-molecular-weight a-1,4 Glucose Polymer that is approved in Europe for use as an intra-operative lavage and a post-operative instillate to reduce the occurrence of post-surgery intra-abdominal adhesions. There are no randomized trials on the use of this solution to prevent adhesions after ASIO operation in current medical literature. The current clinical study evaluates the safety and effectiveness of Icodextrin 4% for decreasing the incidence, extent, and severity of adhesions in patients after abdominal surgery for ASIO.