20.109(F12) Pre-Proposal: Viral mitigation of insulin resistance

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Personal health is of great concern to today's society, especially in relation to weight loss. The rate of Type 2 diabetes in the human population has increased alongside the rate of obesity; it has been clear for some time that excessive weight gain can lead to insulin resistance which is a direct cause of Type 2 diabetes. Presently, the accepted method of prevention and alleviation of obesity and its related ailments is diet and exercise. Drug based weight-loss methods have not been exhaustively explored; of the drugs that have been explored, very few act directly on the adipose cells and the products they secrete. Because mouse adipocytes have been implicated in accelerating the development of insulin resistance through the production of resistin and because increased levels of resisitin can be found in humans that are insulin resistant, the formation of a new therapy that targets resistin could be beneficial in preventing and/or reducing the degree of insulin resistance in any given individual.
Personal health is of great concern to today's society, especially in relation to weight loss. The rate of Type 2 diabetes in the human population has increased alongside the rate of obesity; it has been clear for some time that excessive weight gain can lead to insulin resistance which is a direct cause of Type 2 diabetes. Presently, the accepted method of prevention and alleviation of obesity and its related ailments is diet and exercise. Drug based weight-loss methods have not been exhaustively explored; of the drugs that have been explored, very few act directly on the adipose cells and the products they secrete. Because mouse adipocytes have been implicated in accelerating the development of insulin resistance through the production of resistin and because increased levels of resisitin can be found in humans that are insulin resistant, the formation of a new therapy that targets resistin could be beneficial in preventing and/or reducing the degree of insulin resistance in any given individual.
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Our experiment aims to test if neutralization of resistin via a humoral response can effectively slow the onset of and/or treat insulin resistance in mice. This will be done using a synthetically created system inserted into muscle cells via immunoprophylaxis. The synthetic system will be self regulating and will turn on only when there is an excess of Resistin. When on, the system will produce monoclonal antibodies for resistin when the levels reach a certain threshold, the antibodies will bind to the resistin and prevent it from binding to one of the several receptors of its downstream effectors (such as the receptor ROR1) that may lead to insulin resistance. After the system is introduced into mice that already show symptoms similar to type 2 diabetes, we hope that introducing this potentially long acting therapy that will show a decrease in insulin resistance when given an insulin test. We will test over long periods of time (up 90 days) to monitor how the resistin levels in the blood change at certain time points after the therapy is introduced. We will also periodically perform insulin tests (inject the mice with insulin, test how long they take to stabilize to baseline levels) to get gauges of how resistant the mice are, if at all to the insulin test while being treated with the synthetic system. If we can confirm that downregulating the activity of resistin reduces the level of resistin in the blood and has an effect on insulin resistance, there may be potential for using this therapy for insulin resistance in humans as well.
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Our experiment aims to test if neutralization of resistin via a humoral response can effectively slow the onset of and/or treat insulin resistance in mice. This will be done using a synthetically created system inserted into muscle cells via immunoprophylaxis. The synthetic system will be self regulating and will turn on only when there is an excess of Resistin. When on, the system will produce monoclonal antibodies for resistin when the levels reach a certain threshold, the antibodies will bind to the resistin and prevent it from binding to one of the several receptors of its downstream effectors (such as the receptor ROR1) that may lead to insulin resistance. Upon introducing the system into mice that already show symptoms similar to type 2 diabetes, we hope that this potentially long acting therapy will result a decrease in resistin in the blood as well as a decrease in insulin resistance. We will test over long periods of time (up 90 days) to monitor how the resistin levels in the blood change at certain time points after the therapy is introduced. We will also periodically perform insulin tests (inject the mice with insulin, test how long they take to stabilize to baseline levels) to get gauges of how resistant the mice are, if at all to the insulin test while being treated with the synthetic system. If we can confirm that downregulating the activity of resistin reduces the level of resistin in the blood and has an effect on insulin resistance, there may be potential for using this therapy for insulin resistance in humans as well.
==A sketch==
==A sketch==
[[Image:Preproposal_Diagram.jpg]]
[[Image:Preproposal_Diagram.jpg]]

Revision as of 06:46, 29 November 2012

Contents

Investigators

  • Stanley Gill
  • Amy Liu
  • T/R 20.109 Lab
  • Team Yellow

Title of Proposed Project

Antibody-based Regulation of Resistin Levels through a Synthetic Circuit Injected via Vector Immunoprophylaxis

Project Summary

One of the hallmark characteristics of obesity and Type 2 diabetes is insulin resistance. Resistin, a peptide produced by endocrine adipocytes in mice, has been implicated in increasing the likelihood of insulin resistance and is present in high levels in the blood of obese patients. Here, we explore that the introduction of a regulated synthetic system that produces antibodies against resistin may stave off insulin resistance, alleviating and preventing the development of Type 2 diabetes.

Introduction

ONE PARAGRAPH and at least TWO REFERENCES

  • What is known about this field
  • Why is this field important

Your idea

Personal health is of great concern to today's society, especially in relation to weight loss. The rate of Type 2 diabetes in the human population has increased alongside the rate of obesity; it has been clear for some time that excessive weight gain can lead to insulin resistance which is a direct cause of Type 2 diabetes. Presently, the accepted method of prevention and alleviation of obesity and its related ailments is diet and exercise. Drug based weight-loss methods have not been exhaustively explored; of the drugs that have been explored, very few act directly on the adipose cells and the products they secrete. Because mouse adipocytes have been implicated in accelerating the development of insulin resistance through the production of resistin and because increased levels of resisitin can be found in humans that are insulin resistant, the formation of a new therapy that targets resistin could be beneficial in preventing and/or reducing the degree of insulin resistance in any given individual.

Our experiment aims to test if neutralization of resistin via a humoral response can effectively slow the onset of and/or treat insulin resistance in mice. This will be done using a synthetically created system inserted into muscle cells via immunoprophylaxis. The synthetic system will be self regulating and will turn on only when there is an excess of Resistin. When on, the system will produce monoclonal antibodies for resistin when the levels reach a certain threshold, the antibodies will bind to the resistin and prevent it from binding to one of the several receptors of its downstream effectors (such as the receptor ROR1) that may lead to insulin resistance. Upon introducing the system into mice that already show symptoms similar to type 2 diabetes, we hope that this potentially long acting therapy will result a decrease in resistin in the blood as well as a decrease in insulin resistance. We will test over long periods of time (up 90 days) to monitor how the resistin levels in the blood change at certain time points after the therapy is introduced. We will also periodically perform insulin tests (inject the mice with insulin, test how long they take to stabilize to baseline levels) to get gauges of how resistant the mice are, if at all to the insulin test while being treated with the synthetic system. If we can confirm that downregulating the activity of resistin reduces the level of resistin in the blood and has an effect on insulin resistance, there may be potential for using this therapy for insulin resistance in humans as well.

A sketch

Image:Preproposal_Diagram.jpg

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