a) The isoelectric point (pI) of the hormone insulin is 6.5. Suggest a modificat
ID: 31699 • Letter: A
Question
a) The isoelectric point (pI) of the hormone insulin is 6.5. Suggest a modification of the insulin Bchain that makes it more insoluble at physiological pH, without significantly affecting its binding to the Insulin Receptor (IR)
b) Suggest a protein target for a drug thats effects would complement exogenous delivery of insulin in Type 2 Diabetes. Justify your answer.
c) An insulininduced signaling assay has been developed with the use of cancer HeLa cells. Assess briefly the reliability of this assay
Explanation / Answer
a) The best modification would be the addition of two arginines at the Cterminus of the Bchain (B30). This part of the hormone is not crucial for its interactions with IR. The positively charged arginines would elevate insulin pI towards physiological pH of 7.5, making this analogues less soluble (hence slower acting)
b) The best target here would be one of the families of NRs: PPARs . They bind fatty acids as hormones, stimulating proliferation and differentiation of the adipose tissue. PPARs agonistlike drug would lead to the development of new adipose cells and more even fat distribution in the body. This will make the adipose tissue more sensitive to insulin, making insulindelivery more effective
c) Cancer cells will likely avoid apoptosis by overexpressing of IGF1R and IGF1/ IGF2 hormones for autostimulation
and autoproliferation (one of the major hallmarks of cancer) as one of the strategies in this process.
IGF1/ IGF2 are very similar in structure (and origin) to insulin and IGF1R is very homologus to IR. All these may lead to crossbinding of IGFs and insulin to their not endogenous receptors, and hijacking of their signaling pathways in pathological states or abundance of one of the hormones or receptors. Hence this assay is not reliable.
Related Questions
Navigate
Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.