February Historical Tidbit: Then and Now: This Month in Endocrine History
Submitted by Evan Graber, DO
In February 1985, Ullrich et al reported the amino acid sequence of the insulin receptor precursor. This allowed for elucidation of the function of the mature receptor as part of the tyrosine kinase family. Similarities between the insulin receptor and receptors of other tyrosine kinase-mediated growth factors were also reported. The entire insulin precursor sequence contained 1370 amino acids, which included a precursor signal sequence, the receptor α-subunit, a precursor processing enzyme cleavage site, and finally the β-subunit sequence.
Now, the importance of the tyrosine kinase function of the insulin receptor has resurfaced as tyrosine kinase inhibitors (TKI’s) have become important tools in the treatment of several cancers. These medications are known to impact glucose metabolism (both hyper- and hypoglycemia). The mechanism by which TKI’s impact glucose homeostasis is not known but is thought to be at least in part to the impact on the tyrosine kinase function of the insulin receptor.