Functional Properties of Two Naturally Occurring Isoforms of the Human Insulin Receptor in Chinese Hamster Ovary Cells

We and others have previously demonstrated that the human insulin receptor messenger RNA (mRNA) is alternatively spliced such that the 36-nucleotide sequence encoded by exon 11 of the receptor gene is included (Exll+) or excluded (Exll-). Although both Exll- and Exll+ insulin receptors which differ in the presence or absence of 12 amino acids in the carboxy-terminal a-subunithave been demonstrated to function as insulin receptors when independently overexpressed and studied, the possibility that subtle functional differences between the two isoforms exist has received limited attention. Given that the relative abundance of the two mRNA transcripts is highly regulated in a tissue-specific manner, differences in the functional properties of the two receptor variants might contribute to tissue-specific differences in insulin receptor function and insulin action that are known to exist. To address this hypothesis, we transfected cDNAs encoding the two receptor isoforms into Chinese hamster ovary (CHO) cells a...