Abstract: The present invention relates to biomarkers and methods of using the same. Specifically, the present invention relates to biomarkers for nonalcoholic fatty liver disease and related disease phenotypes and methods of using the same.

Abstract: The present invention relates to compositions and methods for the treatment of NAFLD. Specifically, the present invention relates to compositions comprising one or more BCDKH agonists and methods of using the same for the treatment of NAFLD.

Abstract: Methods of assessing the risk of cardiovascular disease in a subject by detecting the level of at least one metabolite in a sample from the subject are disclosed herein. The level of the metabolite is indicative of the risk of cardiovascular disease in the subject. The metabolites may be acylcarnitines, amino acids, ketones, free fatty acids or hydroxybutyrate. The cardiovascular disease may be risk of a cardiovascular event, presence of coronary artery disease or risk of development of coronary artery disease.

Abstract: Methods of assessing the risk of cardiovascular disease in a subject by detecting the level of at least one metabolite in a sample from the subject are disclosed herein. The level of the metabolite is indicative of the risk of cardiovascular disease in the subject. The metabolites may be acylcarnitines, amino acids, ketones, free fatty acids or hydroxybutyrate. The cardiovascular disease may be risk of a cardiovascular event, presence of coronary artery disease or risk of development of coronary artery disease.

Abstract: The present invention provides methods for treating lipid-related diseases and disorders, e.g., hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, cardiovascular disease, obesity, and type II diabetes, and for modulating lipid biosynthesis, lipid transport, plasma triglyceride levels and/or plasma cholesterol levels, by modulating the expression or activity of PGC-1?. Methods for identifying compounds which are capable of treating or preventing a lipid-related disease or disorder are also described.

Abstract: The present invention provides a method of stimulating growth of a pancreatic islet beta cell and/or enhancing glucose stimulated insulin secretion of a pancreatic islet beta cell, comprising delivering to the cell an exogenous nucleotide sequence encoding Nkx6.1 transcription factor.

Abstract: Methods of modulating blood glucose levels treating hyperglycemia and related complications and conditions by administration of a VGF biomolecule to a patient in need of such treatment are provided. Methods of enhancing insulin secretion from islet beta cells in a mammal exhibiting reduced insulin secretion by administration of a therapeutically effective amount of a VGF biomolecule are also provided.

Abstract: Methods of assessing the risk of cardiovascular disease in a subject by detecting the level of at least one metabolite in a sample from the subject are disclosed herein. The level of the metabolite is indicative of the risk of cardiovascular disease in the subject. The metabolites may be acylcarnitines, amino acids, ketones, free fatty acids or hydroxybutyrate. The cardiovascular disease may be risk of a cardiovascular event, presence of coronary artery disease or risk of development of coronary artery disease.

Abstract: Methods of modulating blood glucose levels treating hyperglycemia and related complications and conditions by administration of a VGF biomolecule to a patient in need of such treatment are provided. Methods of enhancing insulin secretion from islet beta cells in a mammal exhibiting reduced insulin secretion by administration of a therapeutically effective amount of a VGF biomolecule are also provided.

Abstract: The present invention provides methods for treating lipid-related diseases and disorders, e.g., hyperlipidemia, hyper-triglyceridemia, hypercholesterolemia, cardiovascular disease, obesity, and type II diabetes, and for modulating lipid biosynthesis, lipid transport, plasma triglyceride levels and/or plasma cholesterol levels, by modulating the expression or activity of PGC-1?. Methods for identifying compounds which are capable of treating or preventing a lipid-related disease or disorder are also described.

Abstract: The invention provides reagents and methods for reducing hyperglycemia and caloric intake in a subject in need thereof. Also provided are screening methods for identifying compounds that reduce hyperglycemia and/or caloric intake. Further provides are screening methods for identifying compounds that enhance glycogen synthesis without substantially impairing responsiveness to glycogenolytic signals.

Abstract: The present invention describes the identification of numerous genes, both known and unknown, that play an important role in the ability of cell to respond to glucose stimulation under physiologic conditions. These genes may be used to enhance, stabilize or introduce glucose-responsiveness in a host cell, in particular, a host cell that secretes insulin. In addition, these genes may be used as targets for drug screening and as diagnostic indicators for the loss of glucose-responsiveness.

Abstract: The present invention describes methods and compositions for preventing immuno-cytotoxicity of transplanted cells. The invention provides cells and expression constructs encoding STAT-1&agr; polypeptides that prevent cytokine-mediated cytotoxicity. Thus, the invention provides treatment methods for preventing the rejection of transplanted cells by a host. In a particular embodiment, the invention provides for treatment of diabetes by transplanting into a subject insulinoma cells that secrete insulin in response to glucose and further express STAT-1&agr;, thereby conferring resistance to inflammatory cytokines involved in the cell-rejection response.

Abstract: The present invention a provides methods for production of heterologous polypeptides using a variety recombinantly engineered secretory cell lines. The common feature of these cell lines is the absence of expression of at least one endogenous polypeptide. The host cell machinery normally used to produce the endogenous polypeptide is then usurped for the purpose of making the heterologous polypeptide. Also described are methods engineering cells for high level expression, methods of large scale protein production, and methods for treatment of disease in vivo using viral delivery systems and recombinant cell lines.

Abstract: The present invention relates to methods and compositions for the treatment of diabetes involving free radicals. In particular, the present invention is directed to the treatment or prophylactic intervention of diabetes. The present invention demonstrates that MnSOD can play a protective role against cytokine killing, and provides strategies for engineering cell lines as islet surrogates for transplantation therapy of diabetes mellitus. Further, the present invention shows that &bgr;-cell destruction and dysfunction in adipogenic diabetes is mediated via fatty acids. Methods and compositions for ameliorating this disorder are provided herein.

Abstract: The present invention a provides methods for production of heterologous polypeptides, for example amylin, using recombinantly engineered cell lines. Also described are methods engineering cells for high level expression, methods of large scale heterologous protein production, methods for treatment of disease in vivo using viral delivery systems and recombinant cell lines, and methods for isolating novel amylin receptors.

Abstract: The present invention a provides methods for production of heterologous polypeptides using a variety recombinantly engineered secretory cell lines. The common feature of these cell lines is the absence of expression of at least one endogenous polypeptide. The host cell machinery normally used to produce the endogenous polypeptide is then usurped for the purpose of making the heterologous polypeptide. Also described are methods engineering cells for high level expression, methods of large scale protein production, and methods for treatment of disease in vivo using viral delivery systems and recombinant cell lines.

Abstract: Disclosed are compositions and methods for inhibiting hexokinase enzymes in mammalian cells. Specifically provided are proteins that stimulate the production of trehalose-6-phosphate and their respective genes; hexokinase-specific ribozymes and genes encoding such constructs; and agents that competitively reduce hexokinase activity, e.g., by displacing hexokinase from mitochondria, and their respective genes. The latter group of agents includes inactive hexokinases and fragments thereof that retain mitochondrial binding functions and hexokinase-glucokinase chimeras that further substitute glucokinase activity for hexokinase activity. Mammalian cells including such hexokinase inhibitors, methods of making such cells and various in vitro and in vivo methods of using cells with reduced hexokinase activity are also described herein.

Abstract: Disclosed are compositions and methods for inhibiting hexokinase enzymes in mammalian cells. Specifically provided are proteins that stimulate the production of trehalose-6-phosphate and their respective genes; hexokinase-specific ribozymes and genes encoding such constructs; and agents that competitively reduce hexokinase activity, e.g., by displacing hexokinase from mitochondria, and their respective genes. The latter group of agents includes inactive hexokinases and fragments thereof that retain mitochondrial binding functions and hexokinase-glucokinase chimeras that further substitute glucokinase activity for hexokinase activity. Mammalian cells including such hexokinase inhibitors, methods of making such cells and various in vitro and in vivo methods of using cells with reduced hexokinase activity are also described herein.

Abstract: The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.