The insulin receptor (IR) mediates the actions of insulin and insulin-like growth factors (IGF-I and II). Two IR isoforms result from alternate splicing of exon 11, IR-A (without exon 11) and IR-B (with exon 11). Exon 11 is 36 bp and encodes 12 amino acids (717–729) in the COOH-terminus of the IR alpha-subunit. IR-A has higher binding affinity for insulin and IGF-II than IR-B. Interestingly, IR-A is predominantly expressed in fetal tissues, peripheral nerve, brain and tumours whilst IR-B is expressed primarily in classical insulin sensitive tissues such as adult liver and muscle. Our previous studies showed that in mice, like other species, the IR is expressed throughout preimplantation development. IR-B is expressed throughout the preimplantation period, whilst IR-A is expressed following compaction. Immunofluorescent confocal microsopy using an exon11 specific antiserum revealed IR-B immunoreactivity in cell membranes of zygotes and embryos to the morula stage and concentrated in the trophectoderm of blastocysts. Previous studies have shown that insulin can have proliferative effects prior to compaction.1 Consistent with a functional IR at the 2-cell stage, insulin treatment rapidly increased cytoplasmic staining for IR-B within 5-15 min suggesting IR internalization on binding of insulin, which may be either trafficking to the nucleus for regulation of transcription or bound for degradation. Further investigations are underway to address these two options.
(1)Gardner, H. G., and Kaye, P. L. (1991). Insulin increase cell numbers and morphological development in mouse pre-implantation embryos in vitro. Reprod Fertil Dev 3, 79–91.
LMBD1 Protein Serves as a Specific Adaptor for Insulin Receptor Internalization
