Compositions, methods, and kits relating to resistin
AssigneeThe Trustees of the University of Pennsylvania
InventorMitchell A. Lazar
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Abstract
The invention relates to novel nucleic acids encoding a mammalian resistin gene, and proteins encoded thereby, whose expression is suppressed by the antidiabetic compounds thiazolidinediones. The invention further relates to methods of treating and detecting type 2 diabetes and Syndrome X comprising modulating or detecting resistin expression and/or production and activity of resistin polypeptide.
Claims81
An isolated nucleic acid encoding a mammalian resistin, or a fragment thereof.
An isolated nucleic acid encoding a mammalian resistin, wherein the amino acid sequence of said resistin shares at least about 30% sequence identity with an amino acid sequence of at least one of (SEQ ID NO:2) and (SEQ ID NO:4).
An isolated polypeptide comprising a mammalian resistin.
An antibody that specifically binds with a mammalian resistin polypeptide, or a fragment thereof.
A knock-out targeting vector, said vector comprising a first nucleic acid portion encoding a nucleic acid comprising a sequence 5′ of the open reading frame encoding resistin and a second nucleic acid portion comprising a nucleic acid sequence 3′ of the open reading frame encoding a mammalian resistin.
A method of identifying a compound that affects expression of resistin in a cell, said method comprising contacting a cell with a test compound and comparing the level of resistin expression in said cell with the level of resistin expression in an otherwise identical cell not contacted with said test compound, wherein a higher or lower level of resistin expression in said cell contacted with said test compound compared with the level of resistin expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound affects expression of resistin in a cell.
A method of identifying a compound that reduces expression of resistin in a cell, said method comprising contacting a cell with a test compound and comparing the level of resistin expression in said cell with the level of resistin expression in an otherwise identical cell not contacted with said test compound, wherein a lower level of resistin expression in said cell contacted with said test compound compared with the level of resistin expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound reduces expression of resistin in a cell.
A method of determining whether a test compound is a candidate antidiabetic drug candidate, said method comprising contacting a cell comprising a nucleic encoding resistin with a test compound, and comparing the level of expression of resistin in said cell with the level of expression of resistin in an otherwise identical cell which is not contacted with said test compound, whereby a lower level of expression of resistin in said cell contacted with said test compound compared with the level of expression of resistin in said otherwise identical cell not contacted with said test compound is an indication that said test compound is a candidate antidiabetic drug candidate.
A method of determining whether a test compound is a candidate drug for treatment of Syndrome X, said method comprising contacting a cell comprising a nucleic encoding resistin with a test compound, and comparing the level of expression of resistin in said cell with the level of expression of resistin in an otherwise identical cell which is not contacted with said test compound, whereby a lower level of expression of resistin in said cell contacted with said test compound compared with the level of expression of resistin in said otherwise identical cell not contacted with said test compound is an indication that said test compound is a candidate drug for treatment of Syndrome X.
A method of determining whether a test compound is a candidate antidiabetic drug candidate, said method comprising contacting a cell comprising a PPARγ receptor and a nucleic encoding resistin with a test compound, and comparing the level of expression of resistin in said cell with the level of expression of resistin in an otherwise identical cell which is not contacted with said test compound, whereby a lower level of expression of resistin in said cell contacted with said test compound compared with the level of expression of resistin in said otherwise identical cell not contacted with said test compound is an indication that said test compound is a candidate antidiabetic drug candidate.
A method of increasing glucose uptake by a cell, said method comprising contacting a cell expressing resistin with a resistin-reducing amount of an anti-resistin compound, thereby increasing glucose uptake by said cell.
A method of increasing insulin-stimulated glucose uptake by a cell, said method comprising contacting a cell expressing resistin with insulin and further contacting said cell with a resistin-reducing amount of an anti-resistin compound, thereby increasing insulin-stimulated glucose uptake by said cell.
A method of diagnosing type 2 diabetes in a previously undiagnosed mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of resistin in said biological sample, and comparing the level of resistin in said biological sample with the level of resistin in a biological sample obtained from a like mammal not afflicted with type 2 diabetes, wherein a higher level of resistin in said biological sample from said mammal compared with the level of resistin in said biological sample from said like mammal is an indication that said mammal is afflicted with type 2 diabetes, thereby diagnosing type 2 diabetes in said previously undiagnosed mammal.
A method of diagnosing Syndrome X in a previously undiagnosed mammal, said method comprising obtaining a sample from said mammal, assessing the level of resistin in said sample, and comparing the level of resistin in said sample with the level of resistin in a sample obtained from a like mammal not afflicted with Syndrome X, wherein a higher level of resistin in said sample from said mammal compared with the level of resistin in said sample from said like mammal is an indication that said mammal is afflicted with Syndrome X, thereby diagnosing Syndrome X in said previously undiagnosed mammal.
A method of assessing the effectiveness of a treatment for type 2 diabetes in a mammal, said method comprising assessing the level of resistin in a sample obtained from a mammal prior to treatment of said mammal for type 2 diabetes, and comparing the level of resistin in said sample with the level of resistin in a sample obtained from said mammal during the course of or following treatment for type 2 diabetes, wherein a lower level of resistin in said sample obtained prior to treatment compared with said level of resistin in said sample obtained during the course of or following treatment for type 2 diabetes is an indication of the effectiveness of said treatment for type 2 diabetes in said mammal.
A method of assessing the effectiveness of a treatment for Syndrome X in a mammal, said method comprising assessing the level of resistin in a sample obtained from a mammal prior to treatment of said mammal for Syndrome X, and comparing the level of resistin in said sample with the level of resistin in a sample obtained from said mammal during the course of or following treatment for Syndrome X, wherein a lower level of resistin in said sample obtained prior to treatment compared with said level of resistin in said sample obtained during the course of or following treatment for Syndrome X is an indication of the effectiveness of said treatment for Syndrome X in said mammal.
A method of assessing the response in a mammal to TZD, said method comprising assessing the level of resistin in a sample obtained from a mammal prior to administration of TZD to said mammal, administering TZD to said mammal, and assessing the level of resistin in a sample obtained from said mammal during or after administration of TZD, wherein a higher or lower level of resistin in said sample obtained during or after administration of TZD to said mammal compared with said level of resistin in said sample obtained during or after administration of TZD is an indication of the response to TZD in said mammal, thereby assessing the response to TZD in said mammal.
A method of assessing the response in a mammal to a compound that affects PPARγ-mediated signaling, said method comprising assessing the level of resistin in a sample obtained from a mammal prior to administration of said compound to said mammal, administering said compound to said mammal, assessing the level of resistin in a sample obtained from said mammal during or after administration of said compound, and comparing said level of resistin in said sample obtained during or after administration of said compound to said mammal with said level of resistin in said sample obtained prior to administration of said compound to said mammal, wherein a higher or lower level of resistin in said sample obtained during or after administration of said compound to said mammal compared with said level of resistin in said sample obtained prior to administration of said compound to said mammal is an indication of the response in said mammal to said compound, thereby assessing the response in said mammal to a compound that affects PPARγ-mediated signaling.
A method of detecting a mutation in a resistin allele in a human, said method comprising comparing the nucleic acid sequence encoding resistin of a human suspected of having a mutation in a resistin allele with the nucleic acid sequence encoding resistin obtained from a normal human not having a mutation in a resistin allele, wherein any difference between said nucleic acid sequence of said human suspected of having a mutation in said resistin allele and said nucleic acid sequence encoding resistin of said normal human not having a mutation in said resistin allele detects a mutation in said resistin allele in said human.
A method of detecting a mutation in a resistin allele in a human, said method comprising comparing the genomic nucleic acid sequence encoding resistin of a human suspected of having a mutation in a resistin allele with the genomic nucleic acid sequence encoding resistin obtained from a normal human not having a mutation in a resistin allele, wherein any difference between said genomic nucleic acid sequence of said human suspected of having a mutation in said resistin allele and said genomic nucleic acid sequence encoding resistin of said normal human not having a mutation in said resistin allele detects a mutation in said resistin allele in said human.
A method of increasing blood glucose levels in a mammal, said method comprising administering a effective amount of an isolated resistin polypeptide to said mammal, thereby increasing blood glucose levels in said mammal.
A method of increasing blood sugar level in a mammal, said method comprising administering to said mammal an effective amount of resistin, thereby increasing blood sugar level in said mammal.
A method of increasing blood sugar level in a mammal, said method comprising administering to said mammal an isolated recombinant cell transfected with an isolated nucleic acid encoding resistin wherein said nucleic acid is expressed in said cell, wherein the presence of said recombinant cells in said mammal effects an increased blood sugar level in said mammal.
Dependencies are inferred from the claim text.