Abstract: The present invention relates to improved diagnostic methods for early detection of a risk for developing type 2 diabetes mellitus in humans, and screening assays for therapeutic agents useful in the treatment of type 2 diabetes mellitus, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.

Abstract: Compositions and methods are provided for producing adenine nucleotide translocator (ANT) polypeptides and fusion proteins, including the production and use of recombinant expression constructs having a regulated promoter. ANT ligands and compositions and methods for identifying ANT ligands, agents that bind ANT and agents that interact with ANT are also disclosed.

Abstract: The present invention provides methods for depleting mitochondrial DNA from insulin secreting cells using antiviral compounds, and for producing mitochondrial cytoplasmic hybrid (“cybrid”) cells and animals from mitochondrial DNA depleted cells. Also provided are biological models for diseases associated with altered mitochondrial function, including NIDDM, and methods for diagnosis of such diseases and methods for screening agents useful for treating such diseases. Also provided are biological models and methods for evaluating an antiviral compound for its suitability for use in treating a virally-infected patient having a disease associated with impaired insulin secretion, and for evaluating modifications to antiviral compounds in order to determine if such modifications alter (e.g., ameriolate or exacerbate) undesirable side-effects associated with the antiviral compound.

Abstract: The invention provides compositions and methods for altering insulin secretion using an agent that inhibits calcium efflux via the mitochondrial calcium/sodium antiporter (MCA). Methods of treatment are thereby provided, and are particularly useful for treatment of subjects having, or suspected of being at risk for having, diabetes mellitus. Compositions and methods related to the identification of gene sequences encoding the mitochondrial calcium/sodium antiporter, expression of such sequences and screening assays using expressed MCA products are also provided.

Abstract: Compositions and methods are provided for the treatment of diseases associated with altered mitochondrial function, and in particular, for type 2 diabetes mellitus. Administration of an agent that increases mitochondrial mass, including promotion of mitochondrial biogenesis by induction of a PGC gene (e.g., PGC-1) and/or a nuclear regulatory factor gene (e.g., NRF-1), is also disclosed. Screening assays for agents that regulate such genes involved in mitochondrial biogenesis, and for genes and gene products that are regulated by such genes involved in mitochondrial biogenesis, are also provided.

Abstract: The present invention relates to improved diagnostic methods for early detection of a risk for developing type 2 diabetes mellitus in humans, and screening assays for therapeutic agents useful in the treatment of type 2 diabetes mellitus, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.

Abstract: Compositions and methods are provided for producing adenine nucleotide translocator (ANT) polypeptides and fusion proteins, including the production and use of recombinant expression constructs having a regulated promoter. ANT ligands and compositions and methods for identifying ANT ligands, agents that bind ANT and agents that interact with ANT are also disclosed.

Abstract: The present invention provides methods for depleting mitochondrial DNA from insulin secreting cells using antiviral compounds, and for producing mitochondrial cytoplasmic hybrid (“cybrid”) cells and animals from mitochondrial DNA depleted cells. Also provided are methods for modeling diseases associated with altered mitochondrial function, including NIDDM, and methods for diagnosis of such diseases and methods for screening agents that may be useful for such diseases.

Abstract: Compositions and methods are provided for producing adenine nucleotide translocator (ANT) polypeptides and fusion proteins, including the production and use of recombinant expression constructs having a regulated promoter. ANT ligands and compositions and methods for identifying ANT ligands, agents that bind ANT and agents that interact with ANT are also disclosed.

Abstract: The present invention relates to improved diagnostic methods for early detection of a risk for developing type 2 diabetes mellitus in humans, and screening assays for therapeutic agents useful in the treatment of type 2 diabetes mellitus, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, celullar responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.

Abstract: The present invention relates to improved diagnostic methods for early detection of a risk for developing type 2 diabetes mellitus in humans, and screening assays for therapeutic agents useful in the treatment of type 2 diabetes mellitus, by comparing the levels of one or more indicators of altered mitochondrial function. Indicators of altered mitochondrial function include enzymes such as mitochondrial enzymes and ATP biosynthesis factors. Other indicators of altered mitochondrial function include mitochondrial mass, mitochondrial number and mitochondrial DNA content, cellular responses to elevated intracellular calcium and to apoptogens, and free radical production. Methods of treating, and of stratifying, human patients as such methods relate to disclosed indicators of altered mitchondrial function are also provided.