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

Masashi Kobayashi*, Toshiyasu Sasaoka, Yasumitsu Takata, Osamu Ishibashi, Masaaki Sugibayashi, Yukio Shigeta, Akitaka Hisatomi, Etsuo Nakamura, Mikio Tamaki, Hiroshi Teraoka

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Failure to cleave the interconnecting site between α- and β-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.

Original languageEnglish
Pages (from-to)657-663
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume153
Issue number2
DOIs
StatePublished - 1988/06/16

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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