Method of Treating Insulin Resistance

Abstract

A method of treating hyperglycemia, diabetes, metabolic syndrome, insulin resistance (insulin insensitivity), impaired glucose tolerance, high glucose levels, pulmonary hypertension, and/or a condition arising from any of the foregoing in a patient is provided. The method comprises knocking down mARC2 or mARC1 expression in the patient, or otherwise decreasing mARC2 and mARC1 activity in the patient.

What is claimed is: 
     
         1 . A method of treating diabetes, metabolic syndrome, or insulin resistance-associated pulmonary hypertension in a patient in need thereof, comprising knocking down expression of a mitochondrial amidoxime reducing component (mARC) in a patient, thereby treating diabetes, metabolic syndrome, or insulin resistance-associated pulmonary hypertension in the patient, wherein the mARC is mARC2 or mARC1. 
     
     
         2 . The method of  claim 1 , for treating diabetes in a patient in need thereof, comprising knocking down expression of a mitochondrial amidoxime reducing component (mARC) in a patient, thereby treating diabetes in the patient, wherein the mARC is mARC2 or mARC1. 
     
     
         3 . The method of  claim 1 , comprising treating diabetes in the patient by knocking down expression of the mARC in the patient, thereby reducing plasma insulin levels in the patient. 
     
     
         4 . The method of  claim 1 , wherein the mARC mRNA levels are reduced in a cell of the patient. 
     
     
         5 . The method of  claim 1 , wherein the mARC mRNA levels are reduced by administration of a RNAi agent to the patient. 
     
     
         6 . The method of  claim 5 , wherein the RNAi specifically hybridizes to the nucleic acid of SEQ ID NO: 1 or the nucleic acid of SEQ ID NO: 2. 
     
     
         7 . The method of  claim 5 , wherein the RNAi ranges from 21-33 bases in length and comprises or consists of a sequence GTGCTCATCTCCATCATTTAT (SEQ ID NO: 5), GATGAACTCCTAATTGGTAGT (SEQ ID NO: 6), GAACTCCTAATTGGTAGTGTA (SEQ ID NO: 7), GAGGGATTGACTGAGATCTTA (SEQ ID NO: 8), ACAACAGCAGCAACGATACAT (SEQ ID NO: 9), GATGTGCAGGACGCATGTTAC (SEQ ID NO: 10), GGACCTACTACTGCCTATCAA (SEQ ID NO: 11), GAAGAGTTATCGCCAGTGTGA (SEQ ID NO: 12), GACCCTTCAGAACGAAAGTTA (SEQ ID NO: 13), GGTGTCTCAATGCTTCAATGT (SEQ ID NO: 14), GGCTGGAAGAATATCCTAGAA (SEQ ID NO: 15), or GTGATTTCAGATAGACTACTG (SEQ ID NO: 16). 
     
     
         8 . The method of  claim 2 , wherein the diabetes is type-2 diabetes. 
     
     
         9 . The method of  claim 1 , for treating metabolic syndrome in a patient in need thereof, comprising knocking down expression of a mitochondrial amidoxime reducing component (mARC) in a patient, thereby treating metabolic syndrome in the patient, wherein the mARC is mARC2 or mARC1. 
     
     
         10 . The method of  claim 9 , comprising treating metabolic syndrome in the patient by knocking down expression of the mARC in the patient, thereby reducing plasma insulin levels in the patient. 
     
     
         11 . The method of  claim 9 , wherein the mARC mRNA levels are reduced in a cell of the patient. 
     
     
         12 . The method of  claim 9 , wherein the mARC mRNA levels are reduced by administration of a RNAi agent to the patient. 
     
     
         13 . The method of  claim 12 , wherein the RNAi specifically hybridizes to the nucleic acid of SEQ ID NO: 1 or the nucleic acid of SEQ ID NO: 2. 
     
     
         14 . The method of  claim 12 , wherein the RNAi ranges from 21-33 bases in length and comprises or consists of a sequence GTGCTCATCTCCATCATTTAT (SEQ ID NO: 5), GATGAACTCCTAATTGGTAGT (SEQ ID NO: 6), GAACTCCTAATTGGTAGTGTA (SEQ ID NO: 7), GAGGGATTGACTGAGATCTTA (SEQ ID NO: 8), ACAACAGCAGCAACGATACAT (SEQ ID NO: 9), GATGTGCAGGACGCATGTTAC (SEQ ID NO: 10), GGACCTACTACTGCCTATCAA (SEQ ID NO: 11), GAAGAGTTATCGCCAGTGTGA (SEQ ID NO: 12), GACCCTTCAGAACGAAAGTTA (SEQ ID NO: 13), GGTGTCTCAATGCTTCAATGT (SEQ ID NO: 14), GGCTGGAAGAATATCCTAGAA (SEQ ID NO: 15), or GTGATTTCAGATAGACTACTG (SEQ ID NO: 16). 
     
     
         15 . The method of  claim 1 , for treating insulin resistance-associated pulmonary hypertension in a patient in need thereof, comprising knocking down expression of a mitochondrial amidoxime reducing component (mARC) in a patient, thereby treating insulin resistance-associated pulmonary hypertension in the patient, wherein the mARC is mARC2 or mARC1. 
     
     
         16 . The method of  claim 15 , comprising treating insulin resistance-associated pulmonary hypertension in the patient by knocking down expression of the mARC in the patient, thereby reducing plasma insulin levels in the patient. 
     
     
         17 . The method of  claim 15 , wherein the mARC mRNA levels are reduced in a cell of the patient. 
     
     
         18 . The method of  claim 15 , wherein the mARC mRNA levels are reduced by administration of a RNAi agent to the patient. 
     
     
         19 . The method of  claim 18 , wherein the RNAi specifically hybridizes to the nucleic acid of SEQ ID NO: 1 or the nucleic acid of SEQ ID NO: 2. 
     
     
         20 . The method of  claim 18 , wherein the RNAi ranges from 21-33 bases in length and comprises or consists of a sequence GTGCTCATCTCCATCATTTAT (SEQ ID NO: 5), GATGAACTCCTAATTGGTAGT (SEQ ID NO: 6), GAACTCCTAATTGGTAGTGTA (SEQ ID NO: 7), GAGGGATTGACTGAGATCTTA (SEQ ID NO: 8), ACAACAGCAGCAACGATACAT (SEQ ID NO: 9), GATGTGCAGGACGCATGTTAC (SEQ ID NO: 10), GGACCTACTACTGCCTATCAA (SEQ ID NO: 11), GAAGAGTTATCGCCAGTGTGA (SEQ ID NO: 12), GACCCTTCAGAACGAAAGTTA (SEQ ID NO: 13), GGTGTCTCAATGCTTCAATGT (SEQ ID NO: 14), GGCTGGAAGAATATCCTAGAA (SEQ ID NO: 15), or GTGATTTCAGATAGACTACTG (SEQ ID NO: 16).