Nature: Scientists have β new insulin signal suppressors in cells

On January 27, 2021, the Heiko Lickert team at the Helmholtz Munich Center in Germany published an online article in the journal Nature entitled "Inceptors insulin signalling in β-cells to control glycaemia", which revealed the finding in β cells of a new insulin signaling path factor that controls blood sugar.
in this article, researchers identified 5330417C22Rik mRNA expressed strongly in the embryonic pancreas while identifying new pancreatic regulators.
its associated gene is called the estrogen-induced gene (EIG121, also known as ELAPOR1 or KIAA1324), and in mice its genes are located on chromosome 3, with 22 exons transceiver transprinated through three selective shear variants, translated into a one-way type I transdome protein.
compared with the cysteine-rich domain (CRD) and insulin-like growth factor 1 (IGF1R) of insulin-rich in β cells, the bioinficial analysis of KIAA1324 revealed that the cysteine residue in CRD of the growth factor subject domain 4 is conservative.
addition, KIAA1324 has a ganache 6-phosphate-dependent subject (M6PR) domain similar to cation-dependent M6PR (CD-M6PR) and cation-non-dependent M6PR (CI-M6PR).
because of the similarities between KIAA1324 and INSR, IGF1R, and IGF2R in extracellulation domains and KIAA1324 inhibition functions, the researchers renamed KIAA1324 insulin inhibitor (encoded by gene Iir).
Then, the authors conducted a series of experiments that confirmed the quality and blood sugar control of the β cells regulated by the subject, and found that mice with a lack of the ir-ir-/-gene knock-out showed signs of hypersurgemia and hypoglycemia and died within hours of birth.
this suggests that Iir knockout leads to β cell proliferation and increased mass during pancreatic development, and affects glucose stability after birth.
molecular and cell analysis of Iir-/- mouse embryos and postpartum pancreas showed an increase in activation of INSR-IGF1R in Iir-/- pancreatic tissue, resulting in increased proliferation and mass of β cells.
Again, induced β-cell-specific Iir-/- knock-out in adult mice and ionosomes led to increased activation of INSR-IGF1R and increased proliferation of β cells, thereby increasing glucose tolerance in the body.
team also conducted a mechanism study of its effects and found that the subjects made it possible to mediat the internal swallowing of mesh proteins.
, the subject interacts with INSR-IGF1R to promote the internal swallowing of mesh proteins and desensitate the subject.
the use of monoclonal antibodies for the extracellular domain of the subject blocks this physical interaction, which causes the subject and INSR to remain on the mass membrane, thereby maintaining the inSR-IGF1R in the β cells.
in summary, these results suggest that the subject protects insulin-producing β cells from the activation of the composition pathway and identifies the subject as a potential molecular target for INSR-IGF1R sensitivity and diabetes treatment.
: s1. Ansarullah, Jain, C., Far, F.F. et al. Inceptor counteracts insulin signalling in β-cells to control glycaemia. Nature (2021) [2] [3]