145 results about "Glucokinase" patented technology

Compounds represented by formula (I): as well as their pharmaceutically acceptable salts are disclosed. The compounds are useful as glucokinase activating agents for the treatment of diabetes and related conditions. Compositions and methods of treatment are also included.

The invention provides methods for producing products comprising improved host cells genetically engineered to have uncoupled productive and catabolic pathways. In particular, the present invention provides host cells having a modification in nucleic acid encoding an endogenous enzymatic activity that phosphorylates D-glucose at its 6th carbon and / or a modification of nucleic acid encoding an enzymatic activity that phosphorylates D-gluconate at its 6th carbon. Such improved host cells are used for the production of products, such as, ascorbic acid intermediates. Methods for making and using the improved host cells are provided. Nucleic acid and amino acid sequences for glucokinase and gluconokinase are provided.

The present invention provides a glucokinase protein in which the catalytic activity has been disabled in order to enable its use as a glucose sensor. The catalytically disabled glucokinase protein can be used as the glucose sensor in hand-held glucose monitors and in implantable glucose monitoring devices. The glucose sensor can also be incorporated into biomedical devices for the continuous monitoring of glucose and administration of insulin.

The present invention relates to a compound which has a glucokinase-activating effect and is useful as a therapeutic agent for diabetes mellitus, being represented by a formula (I): [wherein X1 represents a nitrogen atom, sulfur atom, oxygen atom or the like; R1 represents a 6- to 10-membered aryl group, 5- to 7-membered heteroaryl group or the like; D represents an oxygen atom or sulfur atom; R and R3 are the same or different, each representing a hydrogen atom, lower alkyl group or the like; a formula (II) represents an optionally substituted 5- to 7-membered heteroaryl group or the like; a formula (III) represents a monocyclic or bicyclic heteroaryl group] or a pharmaceutically acceptable salt thereof.

The invention discloses a creatine jubase MB isozyme activity detection reagent which comprises sulfide-oxidizing coenzyme, 6-phosphaogluconate dehydrogenase, sulfhydryl reagent, magnesium salt, glucokinase or hexoxinase, anti-CK-M antibody, phosphocreatine, adenosine diphosphate, glucose and glucose-6-phosphate dehydrogenase. The preparation method of the reagent is as follows: dissolving all components in a buffer solution with pH of 5.0 to 9.5. The creatine jubase MB isozyme activity detection reagent can enlarge detection sensitivity several times; and the determination result has high precision and degree of accuracy.

Compounds represented by formula (I):as well as their pharmaceutically acceptable salts are disclosed. The compounds are useful as glucokinase activating agents for the treatment of diabetes and related conditions. Compositions and methods of treatment are also included.

Compounds, pharmaceutical compositions, kits and methods are provided for use with glucokinase that comprise a compound selected from the group consisting of formula (I) wherein the variables are as defined herein.

The invention relates to a high-yield acetyl-glucosamine recombinant bacillus subtilis and a construction method thereof. Bacillus subtilis BSGN6 serves as an original strain, glucokinase encoding gene glck expression and glucose phosphate isomerase encoding gene pgi expression in the bacillus subtilis are regulated by xylose inducible promoters PxylA, moderate expression of glck and pgi genes is controlled, the yield of acetyl-glucosamine in the recombinant bacillus subtilis is greatly improved, and a foundation is laid for further producing glucosamine by modifying the bacillus subtilis in metabolic engineering. The construction method is simple and easy to operate, the yield of acetyl-glucosamine can be greatly improved by the constructed recombinant bacillus subtilis, and the recombinant bacillus subtilis has a good application prospect.

The present invention relates to a compound of formula (I):or a pharmaceutically acceptable salt or solvate thereof, wherein:Ring A is (4-12)-membered heterocyclyl;Ring B is a fused benzene ring selected from the group consisting of:Ring A, ring B, ring C, R1, R1a, R2, R3, R4, L2, n, t, w, and z are as defined in the specification. The invention also relates to pharmaceutical compositions comprising the compounds of formula (I) and methods of treating a condition that is mediated by the modulation of glucokinase, the method comprising administering to a mammal an effective amount of a compound of formula (I).

Methods and compositions for identifying mutations and polymorphisms in mutant genes encoding gene product involved in insulin secretion, for example, hepatocyte nuclear factor-1∝, glucokinase, amylin and mitochondrial DNA are disclosed. Specifically, a microchip comprising a combination of at least two different mutant genes wherein each gene comprises at least one mutation indicative of a predisposition for type-2 diabetes in a member of a Chinese population is disclosed. A kit comprising the microchip, an isolated nucleic acid, primers and probes which are specifically used to screen or identify the mutations in genes of hepatocyte nuclear factor-1∝, glucokinase, amylin and mitochondrial DNA are also disclosed.

The present invention relates to a compound which has a glucokinase-activating effect and is useful as a therapeutic agent for diabetes mellitus, being represented by a formula (I):[wherein X1 represents a nitrogen atom, sulfur atom, oxygen atom or the like; R1 represents a 6- to 10-membered aryl group, 5- to 7-membered heteroaryl group or the like; D represents an oxygen atom or sulfur atom; R2 and R3 are the same or different, each representing a hydrogen atom, lower alkyl group or the like; a formula (II)represents an optionally substituted 5- to 7-membered heteroaryl group or the like; a formula (III)represents a monocyclic or bicyclic heteroaryl group] or a pharmaceutically acceptable salt thereof.

The invention discloses a 3-substituted salicylamide compound, a preparation method, a medicinal composition and application thereof, and particularly relates to 3-substituted salicylamide derivativesexpressed by a general formula I, medicinal salts thereof, hydrate and solvent compounds thereof, polycrystal and eutectic crystal thereof, precursor or derivatives thereof with the same biological function, a preparation method thereof, a composition containing one or more compounds, and application of the compounds in the aspects of treating diseases such as diabetes, obesity and the like related to glucose kinase.

Disclosed is a compound represented by the formula (I) below, which has a glucokinase-activating effect and is thus useful for treatment of diabetes or obesity, or a pharmaceutically acceptable salt thereof.In the formula, R1 represents an aryl or the like; R11 represents an aryl or the like; R2 represents a formyl or the like, R3 represents a C1-6 alkyl or the like; R3 represents a hydrogen atom or the like; Z1 represents —O— or the like; Z2 represents —O— or the like; Y1-Y4 respectively represent a carbon atom or a nitrogen atom; ring A represents a heteroaryl group; X represents a carbon atom or the like; m represents an integer of 0-2; and q represents an integer of 0-2.

The invention discloses a construction method of an engineering strain for generating allulose and an application thereof. The construction method comprises the following steps: increasing content ofintracellular fructose 6-phosphoric acid by reducing enzymatic activity of fructose 6-phosphokinase and glucose 6-phosphate dehydrogenase in corynebacterium glutamicum and enhancing enzymatic activityof glucokinase and glucose 6-phophate isomerase by regulating glucose intracellular metabolism; constructing a synthetic route of allulose composed of 6-aloxone phosphate 3-epimerase and 6-aloxone phosphate phosphorylase; constructing a metabolic pathway of fructose composed of fructose transmittase and fructokinase; constructing a metabolic pathway of glycerinum composed of glycerol transmittase, glycerol dehydrogenase and dihydroxyacetone kinase, thereby acquiring a corynebacterium glutamicum recombinant strain. The strain is capable of metabolizing glycerinum, glucose, fructose or saccharose for synthesizing allulose. Compared with the present reported method for compounding allulose through bioconversion of fructose, the construction method provided by the invention has the advantagesof high conversion rate, low production cost, and the like, and is suitable for large-scale production of allulose.

A compound having the activity of glucokinase activation and being useful for the prevention or treatment of diabetes, etc., represented by the formula: (I) [wherein X is a nitrogen atom, etc.; Y is an oxygen atom, etc.; R<1> is an optionally substituted 5 to 6-membered heteroaryl group, etc.; R<2> is a hydrogen atom or a fluorine atom; and the ring A is an optionally substituted monocyclic or bicyclic heteroaryl group of the formula: (II) ], or a pharmacologically acceptable salt thereof.

A process for the production of fluorinated compound formula (I) comprising fluorination of a protected aminothiazole. Compounds formula (I) are useful in the preparation of activators of glucokinase.

The present invention relates to new compounds of formula (1) exhibiting excellent activity for glucokinase, and pharmaceutical compositions comprising the same as an active ingredient.

The present invention is directed to the identification of a biomarker specifically located in the plasma membrane of pancreatic beta cells. It was selected by a Systems Biology approach on Massively Parallel Signal Sequencing datasets obtained in human islets and Affymetrix microarray datasets on human islets, purified rat primary beta and non beta cells and insulinoma cells. Based on a set of specific features the biomarker is a unique candidate for imaging and targeting strategies to study the pancreatic beta cell mass in health and disease (T1 D, T2D, pancreatic cancers, obesity, islet transplantation, beta cell regeneration). The five specific features of the selected biomarkers are: 1) Preferentially expressed in pancreatic islets as compared to surrounding tissues; 2) Higher expression in pancreatic beta cells than in pancreatic alpha cells or than in other islet non-beta cells; 3) Expression levels in pancreatic beta cells are higher or comparable to glucokinase which is an enzyme specifically expressed in the pancreatic beta cell; 4) Located in the membrane and as such targetable with antibodies, peptides or small molecules which allows imaging, targeting and immunohistochemistry; and 5) Expression is not induced during the process of inflammation of the beta cell mass and the protein is not enriched in T-cells and dendritic cells or in other cells participating in the inflammation process.

The present invention relates generally to a population of cells genetically modified to produce insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells genetically modified to produce insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and / or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and / or toxicity of potential adjunctive treatment regimes.

New gene therapy constructions and compositions are the subject of present invention. The gene therapy compositions consist in adeno-associated vectors which jointly express insulin (Ins) and glucokinase (Gck) genes. The new gene therapy constructions are useful for treatment of diabetes either in dogs or human beings.

The present invention relates generally to a population of cells genetically modified to comprise pancreatic islet glucokinase and capable of producing insulin in a glucose responsive manner and uses thereof. More particularly, the present invention relates to a population of cells so genetically modified capable of producing insulin in response to physiologically relevant levels of glucose and uses thereof. The cells of the present invention are useful in a wide variety of applications, in particular in the context of therapeutic and prophylactic regimes directed to the treatment of diabetes and / or the amelioration of symptoms associated with diabetes, based on the transplantation of the cells of the present invention into mammals requiring treatment. Also facilitated is the design of in vitro based screening systems for testing the therapeutic effectiveness and / or toxicity of potential adjunctive treatment regimes.

The invention belongs to the field of traditional Chinese medicine manufacturing, and relates to application of leonurine to preparation of a medicament for treating 2-type diabetes. Animal experiments prove that the fasting blood glucose of a 2-type diabetes mouse, i.e., a db / db mouse, can be lowered by the leonurine, and the tolerance of oral glucose is improved; and meanwhile, fasting plasma insulin is increased, the plasma triglyceride is reduced and the content of the plasma high-density lipoprotein is increased. Experiment results also show that the expression of liver glucose metabolic enzymes such as glucokinase, glucose-6-phosphatase and phosphoenolpyruvate carboxyl enzyme is adjusted by the leonurine in an Akt dependent mode; and the biological response of an inflammatory mediator, such as generation of TNF (Tumor Necrosis Factor)-alpha, degradation of IkB-alpha and subsequent phosphorylation of NF-kBp65, is suppressed. Through the leonurine, the inflammatory state of the 2-type diabetes can be corrected, and the symptoms of the 2-type diabetes can be improved; and the leonurine can be used as a treatment medicament to be applied to the treatment of the 2-type diabetes.

Compounds having glucokinase activating effects and being useful as treatments for diabetes, which are represented by the following formula (I):[wherein X1 represents oxygen, etc., X2 represents oxygen, etc., R1 represents a group on Ring A such as alkylsulfonyl, etc., R2 represents C3-7 cyclic alkyl optionally substituted with a halogen, etc., R3 represents a substituent on Ring B such as lower alkyl, etc., formula (II):[Chemical Formula 1]represents 6- to 10-membered aryl, etc., and formula (III):[Formula 1]represents monocyclic or bicyclic heteroaryl optionally having on Ring B a substituent represented by R3 above, wherein the carbon atom of Ring B which is bonded to the nitrogen atom of the amide group of formula (I) forms a C═N bond with the nitrogen atom of the ring],as well as their pharmaceutically acceptable salts.

The present invention relates to the construction of recombinant glucokinase (Sak) and the preparation process of the expression product, and belongs to the field of biotechnology. The Sak of the present invention is Sak derivative with 15 deletion amino acid residues in the N end and comprising 121 amino acids. The modified Sak gene is expressed effectively in colibacillus with expression level 10 % higher than mature glucokinase expression amount and specific activity about 20 % higher than that of mature glucokinase. The separated and purified single component Sak product has expression product with small molecular weight, high specificity and fast thrombolytic speed. The present invention is suitable for industrial production and may be used in prevention and treatment of acute myocardial infarction, cerebral thrombus and other acute thrombotic diseases.

The invention discloses a kit for detecting methylation degree for GCK (glucokinase) gene associated with type 2 diabetes and application thereof. The kit is characterized by comprising a pair of GCK gene methylated specific amplification primers and methylated specific sequencing primers, wherein the upstream primer has the nucleotide sequence shown as SEQ ID NO.1 while the downstream primer has the nucleotide sequence shown as SEQ ID NO.2. The methylated specific sequencing primers are shown as SEQ ID NO.3. The kit has the advantages that the diagnostic kit can conveniently and quickly detect type 2 diabetes in molecular level with high detection efficiency and strong pertinence; and meanwhile, medicines taking GCK gene methylation as a target point are expected to become a novel means for auxiliary diagnosis, detection and screening of type 2 diabetes.

A freeze-dried preparation of recombinant glucokinase in the form free dried powder, injection, lipoplasm, or microcapsule for thrombolytic purpose contains the glucokinase with mutation of amino acids at positions 7, 3 and 43, and one or more of mannitol, phosphate, EDTA and sodium chloride. Its preparing process is also disclosed.

Compounds of a formula (I) and their pharmaceutically-acceptable salts are disclosed. The compounds have glucokinase-activating effect and are therefore useful for treatment of diabetes and obesity. R1 and R2 each independently represent a lower alkyl group; X1 represent a group of a formula (II-1): wherein: R11 and R12 each independently represent a hydrogen atom or a lower alkyl group, or taken together with the nitrogen atom to which they bond, R11 and R12 may form a 4- to 7-membered nitrogen-containing aliphatic ring (one carbon atom constituting the 4- to 7-membered nitrogen-containing aliphatic ring may be replaced by an oxygen atom), or taken together with a carbon atom in (CH2)m, R11 and R12 may form a 4- to 7-membered nitrogen-containing aliphatic ring; m indicates an integer of from 1 to 3.

Disclosed are new compounds of formula (1) exhibiting excellent activity for glucokinase, pharmaceutical compositions having the same as an active ingredient, and a method of using the same as an active ingredient for lowering blood glucose level:in which the substituents are as defined herein.

The invention discloses an engineered strain for producing tagatose and a construction method and application thereof. According to the construction method, by regulating intracellular glucose metabolism, the enzymatic activity of 6-phosphofructokinase in cells is reduced, the enzymatic activity of glucokinase and the enzymatic activity of glucose 6-phosphate isomerase are improved, therefore, thecontent of fructose-6-phosphate in the cells is increased, a tagatose synthesis path composed of tagatose-6-phosphate 3-epimeriase and tagatose-6-phosphate phosphorylase is constructed, and a fructose metabolism path composed of fructose permease and fructokinase is constructed. The glutamic acid corynebacterium recombination strain is obtained and can synthesize tagatose by metabolizing glucose,fructose or saccharose. Compared with currently reported fructose biotransformation tagatose synthesis methods, the construction method of the engineered strain has the advantages of being easy to operate and facilitating separation and is suitable for large-scale tagatose production.

The invention relates to a method for measuring 1,5-anhydroglucitol by oxidase, which can be widely applied in the field of medical and biochemical technologies. The method comprises the following steps of: converting glucose (Glu) in a sample into fructose-6-phosphate (Fru-6-P) by glucokinase (GK) and phosphoglucose isomerase (PGI), and establishing an ATP regeneration system by pyruvate kanise (PK) and phosphoenolpyruvate (PEP) in the system so as to ensure that Glu is converted into Fru-6-P. In the sample, 1,5-AG reacts in the presence of pyranose oxidase (PROD) to produce 1,5-fructosan (1,5-AF) and H2O2, and then H2O2 is colored and quantified via a Trinder's system..