52 results about "AMP-activated protein kinase" patented technology

The present invention relates to compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, and obesity.

The present invention relates to compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, and obesity.

The present invention relates to a method for treating disease or condition susceptible to amelioration by AMPK activators and compounds of formula which are useful to activate AMP-activated protein kinase (AMPK) and the use of the compounds in the prevention or treatment of disease, including pre-diabetes, type 2 diabetes, syndrome X, metabolic syndrome and obesity.

In the invention provides for a method of stimulating or increasing β-cell replication or growth, by contacting a β-cell with an inhibitor of adenosine kinase (ADK), an inhibitor of S-Adenosylhomocysteine hydrolase (SAHH) or an activator of AMP activated protein kinase (AMPK).

Provided is a pharmaceutical or food or drink composition for preventing or treating alcohol-induced fatty liver or steatohepatitis comprising metadoxine (pyridoxol 1-2-pyrrolidone-5-carboxylate) and garlic oil as active ingredients. The concurrent administration of metadoxine and garlic oil according to the present invention exhibits outstandingly superior effects of inhibiting the accumulation of triglyceride and increase of blood AST (aspartate aminotransferase) level in liver el tissue, inhibiting the expression of FAS (fatty acid synthase), CYP2E1 and iNOS (inducible nitric oxide synthase) and inhibiting the deactivation of AMPK (AMP-activated protein kinase), as compared to the administration of metadoxine or garlic oil only.

The present invention relates to the use of AMP-activated protein kinase (AMP-kinase) agonists or adenosine pro-drugs as immune enhancing compounds, as adjuvants in a vaccine or as anti-inflammatory compounds. The invention further relates to a compositions, vaccines and products comprising an immune response eliciting molecule and an immune response enhancing compound, wherein said immune enhancing compound is chosen from the group of AMP-activated protein kinase (AMP-kinase) agonists or adenosine pro-drugs.

The long-term usage of AICR (5-aminio, 4-imidazole carboxamide riboside) to produce sustained metabolic and biological changes in mammals that overcome insulin resistance, i.e., increase insulin sensitivity, and result in benefits in diseases and conditions such as diabetes, hypertension, atherosclerosis, polycystic ovary syndrome and gallstones is described long-term usage of AICAR, particularly intermittent administration, e.g., three days per week, appears to have some of the positive effects of exercise, having an impact on the amount Of food consumed by a subject and resulting in reduced fat build-up and increase in muscle mass. Therefore, AICAR administration has a positive impact in reducing obesity. AICAR can also Prove useful in preventing or treating vascular diseases associated with hyperglycemia, high plasma levels of free fatty acids (FFA) and triglyceride, and insulin resistance by virtue of the fact that this agent activates fatty acid oxidation. Animal tests have Shown that chronic intermittent treatment with AICAR has not resulted in any noticeable toxic effects. AICAR and related compounds are activators of AMP-activated protein kinase (AMPK) and, furthermore, are effective at decreasing malonyl CoA levels in the animal.

Disclosed is an AMPK activating material used for improving and treating metabolic syndrome, in which AMPK (AMP-activated protein kinase) is a main enzyme for regulating an energy sensor and lipid / glucose metabolism in the body. The activation of AMPK inhibits the synthesis of fat and cholesterol, and accelerates the reduction of body fat and blood glucose, thereby improving obesity, diabetes, and hyperlipidaemia. The disclosed AMPK activating material contains, as active ingredients having an improving and treating effect on metabolic syndrome, including obesity, diabetes, and hyperlipidaemia, a novel compound 2α,3β,12β-trihydroxydammar-20(22)-E,24-diene-3-O-[β-D-glucopyranosyl-(1→)-β-D-glucopyranoside], named Damulin A, and a novel compound 2α,3β,12β-trihydroxydammara-20,24-diene-3-O-[β-D-glucopyranosyl-(1→)-β-D-glucopyranoside], named Damulin B. Herein, the contents of damulin A and damulin B (as active indicator ingredients for AMPK activation) can be increased by treating a Gynostemma pentaphyllum extract with high temperature / high pressure. Accordingly, the novel Gynostemma pentaphyllum extract with a significantly increased AMPK activating capability can be used for improving or treating metabolic syndrome, such as obesity, diabetes, and hyperlipidaemia.

The present invention provides a method of more efficiently producing pancreas cells, particularly pancreatic hormone-producing cells, a method of stably producing pancreas cells in a large amount by more efficiently inducing differentiation of stem cells into pancreas cells, a medicament containing a pancreas cells and a screening method using the cells.A method of producing pancreatic hormone-producing cells, including subjecting stem cells to the following steps (1)-(4):(1) a step of cultivating stem cells in a medium containing an activator of activin receptor-like kinase-4,7 and a GSK3 inhibitor(2) a step of cultivating the cells obtained in the aforementioned step (1) in a medium containing an activator of activin receptor-like kinase-4,7(3) a step of cultivating the cells obtained in the aforementioned step (2) in a medium containing any one or more kinds selected from the group consisting of (a) retinoic acid receptor agonists, (b) at least one kind selected from the group consisting of inhibitors of AMP-activated protein kinase and / or activin receptor-like kinase-2,3,6, and BMP antagonists, and (c) inhibitors of activin receptor-like kinase-4,5,7(4) a step of cultivating the cells obtained in the aforementioned step (3).

The present invention relates to a 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignan compound which activates nutmeg-derived AMP-activated protein kinase (AMPK), and to a composition including same as active ingredients for preventing and treating metabolic syndromes such as obesity. More particularly, the present invention relates to an AMPK-activating compound comprising one of the 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignan-based compounds produced by extracting Myristica fragrans with a solution of 30% or less of ethanol and separating and purifying the extracts using chromatography, as expressed in chemical formula 1 below, and to a composition comprising same as an active ingredient for preventing and treating metabolic syndrome caused by AMPK enzyme activation, such as obesity, diabetes, high cholesterol and cardiopulmonary diseases.

The present invention relates to adenine which is useful to activate AMP-activated protein kinase (AMPK) and the use of adenine in the prevention or treatment of conditions or disease and thereby prevent or treat conditions or diseases which can be ameliorated by AMPK in a mammal.

The present invention relates to oxaloacetate compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds, preserving said compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, obesity, cardiovascular disease, Alzheimer's disease, and cancer.

The invention relates to a method of treating obesity in a mammal. The method includes the step of administering a therapeutically effective amount of an AMP-activated protein kinase activator to the mammal. The mammal may be for example, a human, a rat, a mouse, and the like. The AMP-activated protein kinase activator can be subcutaneously injected into the mammal or administered in any other manner that provides for uptake of the AMP-activated protein kinase activator into the cells of the mammal. The activation of the AMP-activated protein kinase activator can produce the benefits of exercise training including the loss of body fat. The invention also relates to a method of treating insulin resistance in a mammal suffering from obesity, type 2 diabetes, or muscle paralysis. To reduce the insulin resistance a therapeutically effective amount of an AMP-activated protein kinase activator is given to the mammal.

The invention concerns carbon dioxide extracts of Curcuma amada (mango ginger), including supercritical carbon dioxide extracts of C. amada; methods for their production; compositions comprising the extracts; methods for treating or delaying the onset of conditions such as cell proliferation disorder (e.g., cancer), inflammation, infection, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, platelet hyper-aggregation, immune disorder such as autoimmune disorder, or neurodegenerative condition; and methods for inhibiting expression of Bcl-2, Bak, and p53 genes; inhibiting expression of the COX-2 and NF-kB genes, inhibiting production of phosphorylated target of rapamycin (TOR), modulating AMP-activated protein kinase (AMPK), inhibiting protein kinase B (AKT) signaling, modulating the Ras / Raf / MEK / ERK signaling pathway, and modulating the Ras / PI3K / PTEN / Akt / mTOR signaling pathway. Another aspect of the invention concerns a method for inhibiting contamination, comprising applying the extract or composition of the invention to a surface. Another aspect of the invention concerns a method for promoting longevity of a cell in vitro or in vivo, comprising contacting a target cell in vitro or in vivo with an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a method for promoting longevity of a subject, comprising administering an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a method for inhibiting the metabolism of a cancer cell, comprising contacting the target cancer cell in vitro or in vivo with an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a kit including the extract or composition; a container containing the extract or composition; and packaging material.

The present invention relates to compounds of general formula I,wherein the group R1, R2, X, Y and Z are defined as in claim 1, which have valuable pharmacological properties, in particular bind to the AMP-activated protein kinase (AMPK) and modulate its activity. The compounds are suitable for treatment and prevention of diseases which can be influenced by this receptor, such as metabolic diseases, in particular diabetes type 2.

Disclosed is a production method of pancreatic hormone-producing cells in a form that mimics the pancreatogenesis, the method comprising subjecting stem cells to the following steps: (1) cultivating stem cells in a medium containing a Rho kinase inhibitor, (2) cultivating the cells obtained in (1) in a medium containing a GSK3 inhibitor, (3) cultivating the cells obtained in (2) in a medium containing GSK3 inhibitor and an activator of activin receptor-like kinase-4,7, (4) forming a cell mass from the cells obtained in (3), and cultivating the cell mass in a suspension state in a medium, (5) cultivating the cells obtained in (4) in a medium containing a retinoic acid receptor agonist, an inhibitor of AMP-activated protein kinase and / or activin receptor-like kinase-2,3,6, an inhibitor of activin receptor-like kinase-4,5,7 and a cell growth factor, and (6) cultivating the cells obtained in (5).

The present invention relates to oxaloacetate compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds, preserving said compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, obesity, cardiovascular disease, Alzheimer's disease, and cancer.

A method of neuroprotection which comprises administration of an AMPK inhibitor to a patient who is experiencing or has experienced a stroke, the compound being an AMPK inhibitor. Treatments with these agents significantly reduce the size of infarcts, and therefore minimize the loss of brain tissue and neurons. Thus, function can be preserved after stroke or ischemic injury in the brain. Similarly, neuronal loss can be minimized in degenerative diseases that cause neuronal compromise by perturbing energy utilization and availability in neurons.

The present invention provides a method of more efficiently producing pancreas cells, particularly pancreatic hormone-producing cells, a method of stably producing pancreas cells in a large amount by more efficiently inducing differentiation of stem cells into pancreas cells, a medicament containing a pancreas cells and a screening method using the cells.A method of producing pancreatic hormone-producing cells, including subjecting stem cells to the following steps (1)-(4):(1) a step of cultivating stem cells in a medium containing an activator of activin receptor-like kinase-4,7 and a GSK3 inhibitor(2) a step of cultivating the cells obtained in the aforementioned step (1) in a medium containing an activator of activin receptor-like kinase-4,7(3) a step of cultivating the cells obtained in the aforementioned step (2) in a medium containing any one or more kinds selected from the group consisting of (a) retinoic acid receptor agonists, (b) at least one kind selected from the group consisting of inhibitors of AMP-activated protein kinase and / or activin receptor-like kinase-2,3,6, and BMP antagonists, and (c) inhibitors of activin receptor-like kinase-4,5,7(4) a step of cultivating the cells obtained in the aforementioned step (3).

The present invention relates to adenine which is useful to activate AMP-activated protein kinase (AMPK) and the use of adenine in the prevention or treatment of conditions or disease and thereby prevent or treat conditions or diseases which can be ameliorated by AMPK in a mammal.

In the invention provides for a method of stimulating or increasing beta-cell replication or growth, by contacting a beta-cell with an inhibitor of adenosine kinase (ADK), an inhibitor of S-Adenosylhomocysteine hydrolase (SAHH) or an activator of AMP activated protein kinase (AMPK).

The subject invention pertains to supercritical carbon dioxide extracts of Commiphora mukul resin (guggul), which can be modified or not modified by some ethanol addition; methods for their production; and methods of use, such as inhibiting HMG-CoA reductase, inhibiting transformation of pre-adipocytes to adipocytes, inhibiting triglyceride storage, promoting insulin sensitivity in adipocytes, treatment of disorders (for example, hypercholesterolemia, hyperlipidemia, hyperglycemia, obesity, metabolic syndrome, cardiovascular disease, atherosclerotic heart disease, autoimmune disorder, insulin resistance, leptin resistance, arthritis, cell proliferation disorder, such as cancer and atherosclerosis; damaged skin, sores, cuts, rashes, bruises, dryness, burns, sunburn, radiation burn, and infection), and regulating or suppressing appetite.

The invention belongs to the technical field of molar-diagnosis and solves the problems that in the prior art, deterioration and metastasis of tumor cells are not known clearly and diagnosis evidencecannot be supplied to tumor metastasis and prognosis diagnosis. The invention provides an application of an AMP-activated protein kinase (AMPK) as a biomarker of tumor metastasis and prognosis diagnosis, and an application of AMPK[alpha]1 as a biomarker for the tumor metastasis and prognosis diagnosis. In the invention, an experiment proves that cancer signals (PI3K, Ras and Her2) inhibiting protein expression of the AMPK[alpha]1 in malignant tumors are matched with clinical data very well, thus proving that the significant low expression of the AMPK[alpha]1 in malignant tumors is a key factorof the metastasis of malignant tumors; with the gene expression level of the AMPK[alpha]1 as an important index for the diagnosis and prognosis of tumor metastasis, the AMPK[alpha]1 can be applied asa biomarker to the tumor metastasis and prognosis diagnosis.

A method of treating type 2 diabetes in a mammal is provided. The method includes the step of administering a therapeutically effective amount of an AMP-activated protein kinase activator to the mammal. The mammal may be for example, a human, a rat, a mouse, and the like. The AMP-activated protein kinase activator can be subcutaneously injected into the mammal or administered in any other manner that provides for uptake of the AMP-activated protein kinase activator into the cells of the mammal. The activation of the AMP-activated protein kinase activator can produce the benefits of exercise training including the translocation of GLUT4 in the muscle cells of the mammal. A method of treating insulin resistance in a mammal is also provided. To treat the insulin resistance a therapeutically effective amount of an AMP-activated protein kinase activator is given to the mammal.

A method of neuroprotection which comprises administration of an AMPK inhibitor to a patient who is experiencing or has experienced a stroke, the compound being an AMPK inhibitor. Treatments with these agents significantly reduce the size of infarcts, and therefore minimize the loss of brain tissue and neurons. Thus, function can be preserved after stroke or ischemic injury in the brain. Similarly, neuronal loss can be minimized in degenerative diseases that cause neuronal compromise by perturbing energy utilization and availability in neurons.

The invention relates to compounds that are direct activators of AMPK (AMP-activated protein kinase) and their use in the treatment of disorders regulated by activation of AMPK. For instance, compounds according to the invention are useful for the treatment of diabetes, metabolic syndrome, obesity, inflammation, cancer and cardiovascular diseases.

The invention belongs to the fields of biology and medicine and discloses a method for generating mitochondria uncoupling and activating adenosine monophosphate activated protein kinase (AMPK). The method is characterized in that horizontal reversed electron transfer of a mitochondrial respiratory chain complex I is caused by oxidation of a sulfur-containing compound through SQR, cross-mitochondrial inner membrane potential is reduced, and thereby mitochondrial uncoupling is generated; by the mitochondrial uncoupling, the synthesis level of ATP in cells can be reduced and further the AMPK is activated. The invention also discloses a method for obtaining a mitochondria uncoupling agent and an AMPK activator based on the SQR. The experiment verifies that the method disclosed by the inventionhas the advantages that firstly, oxidation of the sulfur-containing compound by the SQR is a novel method for generating the mitochondria uncoupling or activating the AMPK; secondly, a novel mitochondria uncoupling agent or the AMPK activator can be obtained on the basis of the SQR; thirdly, an obtained compound has the mitochondria uncoupling of cell specificity or AMPK activating effect as wellas low toxic and side effects, and can be used for treating related diseases.

Disclosed is a production method of pancreatic hormone-producing cells in a form that mimicks the pancreatogenesis, the method comprising subjecting stem cells to the following steps:(1) cultivating stem cells in a medium containing a Rho kinase inhibitor,(2) cultivating the cells obtained in (1) in a medium containing a GSK3 inhibitor,(3) cultivating the cells obtained in (2) in a medium containing GSK3 inhibitor and an activator of activin receptor-like kinase-4,7,(4) forming a cell mass from the cells obtained in (3), and cultivating the cell mass in a suspension state in a medium,(5) cultivating the cells obtained in (4) in a medium containing a retinoic acid receptor agonist, an inhibitor of AMP-activated protein kinase and / or activin receptor-like kinase-2,3,6, an inhibitor of activin receptor-like kinase-4,5,7 and a cell growth factor, and(6) cultivating the cells obtained in (5).