I am looking to stimulate the insulin signaling pathway in a way that does not involve the insulin receptor. Thank you in advance!
Are you trying to increase insulin secretion without acting on insulin receptor? If that's the case, maybe you can try by using GLP-1 receptor agonist?
Mol Cell Endocrinol. 2010 Apr 12;317(1-2):148-53. doi: 10.1016/j.mce.2009.12.027. Epub 2009 Dec 29.
Berberine modulates insulin signaling transduction in insulin-resistant cells.
Liu LZ1, Cheung SC, Lan LL, Ho SK, Xu HX, Chan JC, Tong PC.
check this
This is an interesting question. I am sure that you took into account that the simplest way to make what you wish should be either avoiding insulin into the medium (you are working fully in vitro, I suppose), or, more complicate, blocking insulin receptor (g.e.: please look/evaluate at this purpose the use of simvastatin: https://www.ncbi.nlm.nih.gov/pubmed/27470565) or using cells deleted for the insulin receptor (g.e.: J Biol Chem. 2016 Aug 17. pii: jbc.M116.735738.). Sorry, I have no experience with those treatments or cells. Glucagon at varying concentrations may be also a choice, if you would modulate the insulin receptor activity at selected levels (please look at pubmed for this item). Also, you may think to use some peculiar formulation of amino acids both for interfering backward with the normal activation by insulin of its receptor through allosteric inhibition of anaerobic glycolysis by some amino aicd, still mantaining GLUT-1 and 4 expression on membranes, and another, different, formulation to induce PGC1 alpha mediated mitochondrial biogenesis, which rules downstream dimensions of normal receptor activity of insulin, but also drives increased metabolic effect of insulin on energetic metabolism (increased citochrome C, respiratory chain activity and full pyruvate oxydation). Good luck, if you succeed you will disentangle a most complicate knot!
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