Insulin resistance by unprocessed insulin proreceptors point mutation at the cleavage site.

Abstract

Failure to cleave the interconnecting site between alpha- and beta-subunit produced insulin proreceptors in the plasma membranes which had markedly low affinity to insulin, leading to extreme insulin resistance in a patient. We performed cDNA sequence analysis of the cleavage site of the insulin proreceptor from the patient. Polymerase chain reaction was used to obtain large amount of cDNA coding for the region including the interconnecting site. A thermostable DNA polymerase, Taq polymerase, successfully produced enough amount of cDNA of the region to be sequenced. The results showed AGG (Arg) to AGT (Ser) point mutation, resulting in the change of interconnecting sequence of the two subunits from -Arg-Lys-Arg-Arg- to -Arg-Lys-Arg-Ser-. These results suggest that the tertial structure change of the cleavage site leads to production of unprocessed insulin proreceptors.

• Authors: M Kobayashi, T Sasaoka, Y Takata, O Ishibashi, M Sugibayashi, Y Shigeta, A Hisatomi, E Nakamura, M Tamaki, H Teraoka
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 153 Issue 2 Pg. 657-63 (Jun 16 1988) ISSN: 0006-291X [Print] United States
• PMID: 3289535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Protein Precursors
• Receptor, Insulin

Topics

• Base Sequence
• Cell Membrane (metabolism)
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Molecular Weight
• Mutation
• Protein Precursors (metabolism)
• Protein Processing, Post-Translational
• Receptor, Insulin (genetics, metabolism)
• Structure-Activity Relationship