Post by peppy on May 21, 2016 12:19:27 GMT -5
More details about "cancer concerns"---
We should be concerned about the glargines----
Increased Intrinsic Disorder Propensity in Some Insulin Analogues as a Marker of their Increased Mitogenicity
In other words, this report discusses the evaluation of insulin analogues in terms of confirmational stability, ie how flexible, unraveled, or exposed----
Genetic engineering of DNA was used to change the amino acid sequence of natural insulin to produce insulin analogues or IR binding agonists with altered physiological properties, such as absorption, distribution, metabolism, and excretion characteristics of insulin. . .
These modifications of native insulin were needed mostly to affect the dissociation rate of zinc-bound insulin hexamers (which is a natural form of this protein that is not able to interact with IR) to biologically active monomers. As a result, modifications used in the Glulisine, Aspart, and Lispro were introduced to generate short-acting insulin analogues (i.e., analogues that dissociate more rapidly than the native insulin following injection), whereas modifications used in Glargine, Detemir, and Degludec were made to produce long-acting insulin analogues (i.e., insulins with delayed absorption or a prolonged duration of action)
These modifications of native insulin were needed mostly to affect the dissociation rate of zinc-bound insulin hexamers (which is a natural form of this protein that is not able to interact with IR) to biologically active monomers. As a result, modifications used in the Glulisine, Aspart, and Lispro were introduced to generate short-acting insulin analogues (i.e., analogues that dissociate more rapidly than the native insulin following injection), whereas modifications used in Glargine, Detemir, and Degludec were made to produce long-acting insulin analogues (i.e., insulins with delayed absorption or a prolonged duration of action)
It was pointed out that the insulin analogues with the substantially increased affinity for the IGF1 receptors might possess an increased potency to stimulate proliferation of cells. Because many of the primary tumors and malignant cells are characterized by an increased expression of IGF1 receptors, the aforementioned higher affinities of some insulin analogues to these receptors could be of clinical importance.
. . . solution structures of human insulin and IGFs possess rather different dynamic properties, with insulin being the least flexible and IGF1 being the most dynamic molecule.
Curiously, Glargine and its modified form, AspB10/Glargine, which are known to have the highest affinity to the IGF1 receptor in vitro among all insulin analogues, are characterized by the highest levels of intrinsic disorder/flexibility in their central regions.
This observation suggests that the analysis of disorder profiles might have some predictive power for evaluation of the mitogenicity/carcinogenicity of insulin analogues.
Therefore, the use of the corresponding computational tools for sequence-based evaluation of intrinsic disorder predisposition is recommended while developing new insulin analogues.
This observation suggests that the analysis of disorder profiles might have some predictive power for evaluation of the mitogenicity/carcinogenicity of insulin analogues.
Therefore, the use of the corresponding computational tools for sequence-based evaluation of intrinsic disorder predisposition is recommended while developing new insulin analogues.
Sci Rep. 2016; 6: 23320.
Published online 2016 Mar 17. doi: 10.1038/srep23320
Elrashdy M. Redwan,a,1,2 Moustafa H. Linjawi,3 and Vladimir N. Uverskyb,1,4,5
1Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
2Therapeutic and Protective Proteins Laboratory, Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications, New Borg EL-Arab 21934, Alexandria, Egypt
3Department of Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
4Department of Molecular Medicine and USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
5Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation, Russia
aEmail: moc.oohay@1691nawder
bEmail: ude.fsu.htlaeh@yksrevuv
Good work cm5.
Plenty of people have bought the story, insulin and insulin analogues are the same molecules our bodies make. oh, ha ha.
As you pointed out, it is the best insulin e.coli can make for us and it is further engineered, for patents.
People that believe subq delivery of these molecules are safer than inhalation are difficult to argue with as it is their bodies and their minds, they get to decide.
I do not buy that subj delivery of insulin is safer than inhalation. that is just me.
too bad people do not know reports about people feeling better on technosphere insulin, a monomer.
To be fair to aged, the concern is the effect of insulin, a hormone on cells, lung cells. The alveoli. That is where the gas exchange is.
Pep