Reducing blood glucose, insulin resistance, or hyperlipidemia through rlip76 partial depletion

Abstract

Partial depletion of RLIP76 in p53 deficient living subject has shown many health benefits. In one embodiment, partical Rlip depletion is used to prevent or treat cancer in p53 deficient living subjects. In another embodiment, partial Rlip depletion is used for reversion of DNA-methylation abnormalities caused by the lack of p53 to normal in p53 deficient living subjects. In yet another embodiment, partial Rlip depletion is used in reduction of blood glucose, insulin-resistance, hyperlipidemina, or any combination thereof in p53 deficient living subjects. Methods of using liposome containing anti-sense nucleic acid or double stranded siRNA to partially deplete RLIP76 and thus treat p53 deficient subject are disclosed. The approaches described herein can be especially helpful in preventing cancer in Li-Fraumeni patients.

We claim: 
     
         1 . A method of reducing blood glucose, insulin resistance, hyperlipidemia, or any combination thereof in a subject, the method comprising administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject. 
     
     
         2 . The method of  claim 1 , wherein the liposome inhibitory RNA molecule targets nucleotides encoding a region of RLIP76 having a sequence of SEQ ID NO.: 1. 
     
     
         3 . The method of  claim 1 , wherein the liposome inhibitory RNA molecule is an anti-sense molecule having a nucleic acid sequence of SEQ ID NO.: 2, and wherein the anti-sense molecule targets nucleotides encoding a region of RLIP76 having a sequence of SEQ ID NO.: 1. 
     
     
         4 . The method of  claim 1 , wherein the liposome inhibitory RNA molecule is an siRNA molecule comprised of SEQ ID NO: 3 and SEQ ID NO: 6, and wherein the siRNA molecule targets nucleotides encoding a region of RLIP76 having a sequence of SEQ ID NO.: 1. 
     
     
         5 . The method of  claim 1 , wherein the liposome inhibitory RNA molecule is complementary to an mRNA that encodes SEQ ID NO.: 4, and wherein the inhibitory RNA molecule targets nucleotides encoding a region of RLIP76 having a sequence of SEQ ID NO.: 1. 
     
     
         6 . The method of  claim 1 , wherein at least 20% of the total RLIP76 in the subject is inhibited. 
     
     
         7 . The method of  claim 1 , wherein at least 22.5-25%, 22.5-27.5%, 27.5-30%, 30-32.5%, 32.5-35%, 35-37.5%, 37.5-40%, 40-42.5%, 42.5-45%, 45-47.5%, 47.5-50%, 50-52.5%, 52.5-55%, 55-57.5%, 57.5-60%, 60-62.5%, 62.5-65%, 65-67.5%, 67.5-70%, 70-72.5%, 72.5-75%, 75-77.5%, or 77.5-80% of the total RLIP76 in the subject is inhibited. 
     
     
         8 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces blood glucose, and wherein blood glucose is reduced by at least 50%. 
     
     
         9 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces insulin resistance, and wherein insulin resistance is reduced by at least 50%. 
     
     
         10 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces hyperlipidemia, and wherein hyperlipidemia is reduced by at least 50%. 
     
     
         11 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces blood glucose and insulin resistance, and wherein blood glucose and insulin resistance are reduced by at least 50%. 
     
     
         12 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces blood glucose and hyperlipidemia, and wherein blood glucose and hyperlipidemia are reduced by at least 50%. 
     
     
         13 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces insulin resistance and hyperlipidemia, and wherein insulin resistance and hyperlipidemia are reduced by at least 50%. 
     
     
         14 . The method of  claim 1 , wherein administering an effective amount of a composition comprising a liposome inhibitory RNA molecule into the subject to at least partially inhibit RLIP76 in the subject reduces blood glucose, insulin resistance, and hyperlipidemia, and wherein blood glucose, insulin resistance, and hyperlipidemia are reduced by at least 50%. 
     
     
         15 . The method of  claim 1 , wherein the effective amount comprises a dose of 0.1-30 mg/kg of the subject. 
     
     
         16 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         17 . The method of  claim 1 , wherein administration of the composition is repeated at predetermined intervals to effect chronic partial inhibition of RLIP76 in the subject such that blood glucose, insulin resistance, hyperlipidemia, or any combination thereof in the subject is chronically reduced. 
     
     
         18 . The method of  claim 17 , wherein the total RLIP76 in the subject is chronically inhibited by at least 20%. 
     
     
         19 . The method of  claim 1 , wherein the composition is administered every day, every week, every month, or every year. 
     
     
         20 . A method of reducing blood glucose, insulin resistance, hyperlipidemia, or any combination thereof in a subject, the method comprising administering an effective amount of a composition comprising an anti-RLIP antibody into the subject to at least partially inhibit RLIP76 in the subject.