Category
Poster - Theoretical Proposal
Description
Over 500 million people worldwide, including 36 million Americans, are affected by type II diabetes, a metabolic disease characterized by insulin resistance and hyperglycemia. Complications associated with this disease include but are not limited to retinopathy, cardiovascular disease, neuropathy, and nephropathy. One of the major causes of insulin resistance stems from the protein IRS-1’s insensitivity to activate downstream events when insulin binds to its receptor. Although there are numerous proteins that downregulate IRS-1 through serine phosphorylation, p300, a broad histone acetyltransferase responsible for the regulation of hundreds of transcriptions factors, can also inhibit IRS-1 through acetylation. Recent studies revealed that p300 inhibition using 20 m of C646 promotes insulin sensitivity. Such high concentrations of C646 may significantly interfere with other cellular processes. Our study aims to use lower concentrations of C646 combined with other natural compounds known to reverse insulin resistance. For example, cinnamon and curcumin are known to improve insulin resistance, but their effect of IRS-1 has not been directly investigated. Treatment with these compounds in conjunction with lower concentrations of C646 will potentially result in a more favorable outcome. For this investigation, we will culture lines of L6 rat cells, human HepG2 cells, and 3T3-L1 mouse cells and render them insulin resistant using various concentration of palmitic acid, insulin, and glucose. Each line will then be treated with cinnamon, curcumin, and common anti-diabetic medications in combination with C646. The results of this experiment have promising potential and significance in understanding insulin resistance in the IRS-1 pathway. Future research will involve treatment in an insulin resistant mouse model. These treatments may provide better understanding in novel ways to restore insulin sensitivity.
The Effect of Post-Translational Modifications of IRS-1 on Insulin Sensitivity
Poster - Theoretical Proposal
Over 500 million people worldwide, including 36 million Americans, are affected by type II diabetes, a metabolic disease characterized by insulin resistance and hyperglycemia. Complications associated with this disease include but are not limited to retinopathy, cardiovascular disease, neuropathy, and nephropathy. One of the major causes of insulin resistance stems from the protein IRS-1’s insensitivity to activate downstream events when insulin binds to its receptor. Although there are numerous proteins that downregulate IRS-1 through serine phosphorylation, p300, a broad histone acetyltransferase responsible for the regulation of hundreds of transcriptions factors, can also inhibit IRS-1 through acetylation. Recent studies revealed that p300 inhibition using 20 m of C646 promotes insulin sensitivity. Such high concentrations of C646 may significantly interfere with other cellular processes. Our study aims to use lower concentrations of C646 combined with other natural compounds known to reverse insulin resistance. For example, cinnamon and curcumin are known to improve insulin resistance, but their effect of IRS-1 has not been directly investigated. Treatment with these compounds in conjunction with lower concentrations of C646 will potentially result in a more favorable outcome. For this investigation, we will culture lines of L6 rat cells, human HepG2 cells, and 3T3-L1 mouse cells and render them insulin resistant using various concentration of palmitic acid, insulin, and glucose. Each line will then be treated with cinnamon, curcumin, and common anti-diabetic medications in combination with C646. The results of this experiment have promising potential and significance in understanding insulin resistance in the IRS-1 pathway. Future research will involve treatment in an insulin resistant mouse model. These treatments may provide better understanding in novel ways to restore insulin sensitivity.
Comments
Undergraduate