title: Differences in the ratio of RNA encoding two isoforms of the insulin receptor between control and NIDDM patients. The RNA variant without Exon 11 predominates in both groups.
abstract: Two alternative forms of the insulin receptor with different affinities for insulin are expressed as a result of alternative splicing of RNA corresponding to exon 11 of the IR gene. The percentage of IR-RNA molecules without exon 11, encoding the high-affinity isoform, was determined by cDNA-mediated PCR amplification of RNA extracts from the quadriceps femoris muscle of healthy control subjects (n = 9) and NIDDM patients (n = 7). In both patients and control individuals, a majority of the IR-RNA molecules contained exon 11. In addition, the proportion of IR-RNA molecules without exon 11 was decreased in patients (21 +/- 1%) compared with control subjects (31 +/- 3%) (P = 0.018). Careful investigation of the kinetics of the PCR-based assay system, as well as the conditions for separation of the PCR products, allowed us to suggest a possible explanation of the discrepant results concerning the alternative splicing presented in previous reports. The diabetic subjects as a group had higher fasting insulin levels and lower insulin-mediated glucose uptake during a euglycemic-hyperinsulinemic clamp (P = 0.042). However, identification of the regulatory pathways leading to the splicing alteration in NIDDM patients requires further investigation.
authors.affiliation: Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Norgren
authors.forename: J
authors.initials: J
authors.lastname: Zierath
authors.forename: D
authors.initials: D
authors.lastname: Galuska
authors.forename: H
authors.initials: H
authors.lastname: Wallberg-Henriksson
authors.forename: H
authors.initials: H
authors.lastname: Luthman
mesh_terms: D017398:Alternative Splicing; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D005091:Exons; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*; D012016:Reference Values; D014407:Tumor Cells, Cultured
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D012313:RNA; D011972:Receptor, Insulin