Significant change in insulin production, glucose tolerance and ER stress signaling in transgenic mice coexpressing insulin-siRNA and human IDE

Dae Youn Hwang, Sujin Seo, Yongkyu Kim, Chuelkyu Kim, Sunbo Shim, Seungwan Jee, Suhae Lee, Jisoon Sin, Junyong Cho, Byeong Cheol Kang, Insurk Jang, Jungsik Cho

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Abstract

The dual expression system for the suppression and clearance of insulin has not been previously used to produce transgenic mice for diabetes-related disease. The aim of this study was to produce new transgenic mice coexpressing specific insulin small interfering RNA (siRNA) sequences and the human insulin degrading enzyme (hIDE) gene in order to examine the diabetes-like phenotype. To achieve this, a new lineage of transgenic mice was produced by the microinjection of the dual expression constructs (pH1/siRNA insulin - CMV/hIDE) into mouse fertilized eggs. The results showed that overexpressing the insulin siRNA and hIDE genes resulted in the induction of the human enzyme, impaired glucose tolerance and lower serum insulin levels compared to the Non-Tg mice. Moreover, the Tg mice aged 20 weeks had a significantly activated ER stress signaling compared to their Non-Tg counterparts, which may be associated with the suppression of insulin production in the pancreas and the degradation of insulin in the liver, respectively. Therefore, insulin-suppressed transgenic mice can be used to examine diabetes as a new diabetes-like phenotype model, which results in a lower level of circulating insulin without the destruction of pancreatic islets.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalInternational Journal of Molecular Medicine
Volume19
Issue number1
StatePublished - 1 Jan 2007

Fingerprint

Small Interfering RNA
Transgenic Mice
Insulin
Glucose
Insulysin
Phenotype
Enzyme Induction
Gene Order
Glucose Intolerance
Zygote
Microinjections
Islets of Langerhans
Pancreas
Liver
Serum
Genes

Keywords

  • Diabetes
  • Insulin
  • Transgenic mice
  • hIDE
  • siRNA

Cite this

Hwang, Dae Youn ; Seo, Sujin ; Kim, Yongkyu ; Kim, Chuelkyu ; Shim, Sunbo ; Jee, Seungwan ; Lee, Suhae ; Sin, Jisoon ; Cho, Junyong ; Kang, Byeong Cheol ; Jang, Insurk ; Cho, Jungsik. / Significant change in insulin production, glucose tolerance and ER stress signaling in transgenic mice coexpressing insulin-siRNA and human IDE. In: International Journal of Molecular Medicine. 2007 ; Vol. 19, No. 1. pp. 65-73.
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abstract = "The dual expression system for the suppression and clearance of insulin has not been previously used to produce transgenic mice for diabetes-related disease. The aim of this study was to produce new transgenic mice coexpressing specific insulin small interfering RNA (siRNA) sequences and the human insulin degrading enzyme (hIDE) gene in order to examine the diabetes-like phenotype. To achieve this, a new lineage of transgenic mice was produced by the microinjection of the dual expression constructs (pH1/siRNA insulin - CMV/hIDE) into mouse fertilized eggs. The results showed that overexpressing the insulin siRNA and hIDE genes resulted in the induction of the human enzyme, impaired glucose tolerance and lower serum insulin levels compared to the Non-Tg mice. Moreover, the Tg mice aged 20 weeks had a significantly activated ER stress signaling compared to their Non-Tg counterparts, which may be associated with the suppression of insulin production in the pancreas and the degradation of insulin in the liver, respectively. Therefore, insulin-suppressed transgenic mice can be used to examine diabetes as a new diabetes-like phenotype model, which results in a lower level of circulating insulin without the destruction of pancreatic islets.",
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Hwang, DY, Seo, S, Kim, Y, Kim, C, Shim, S, Jee, S, Lee, S, Sin, J, Cho, J, Kang, BC, Jang, I & Cho, J 2007, 'Significant change in insulin production, glucose tolerance and ER stress signaling in transgenic mice coexpressing insulin-siRNA and human IDE', International Journal of Molecular Medicine, vol. 19, no. 1, pp. 65-73.

Significant change in insulin production, glucose tolerance and ER stress signaling in transgenic mice coexpressing insulin-siRNA and human IDE. / Hwang, Dae Youn; Seo, Sujin; Kim, Yongkyu; Kim, Chuelkyu; Shim, Sunbo; Jee, Seungwan; Lee, Suhae; Sin, Jisoon; Cho, Junyong; Kang, Byeong Cheol; Jang, Insurk; Cho, Jungsik.

In: International Journal of Molecular Medicine, Vol. 19, No. 1, 01.01.2007, p. 65-73.

Research output: Contribution to journalArticleResearchpeer-review

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