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Biologically active human islet amyloid polypeptide/amylin in transgenic mice
K L van Hulst1, W Born, R Muff
1Department of Internal Medicine, Utrecht University, The Netherlands.
European Journal of Endocrinology
|January 1, 1997
Summary
Transgenic mice overexpressing human islet amyloid polypeptide (hIAPP) in pancreatic beta cells produce biologically active hIAPP. These mice are validated for studying hIAPP
Area of Science:
- Endocrinology
- Molecular Biology
- Biochemistry
Background:
- Human islet amyloid polypeptide (hIAPP), or amylin, is a pancreatic beta cell protein linked to type 2 diabetes.
- Understanding hIAPP's role in islet amyloid formation is crucial for diabetes research.
Purpose of the Study:
- To generate and validate transgenic mice overexpressing hIAPP for studying its physiological and pathological roles.
- To assess the biological activity of human and mouse IAPP in vivo.
Main Methods:
- Generated transgenic mice overexpressing hIAPP mRNA in pancreatic beta cells.
- Analyzed pancreatic and plasma extracts using HPLC and radioimmunoassay.
- Assessed biological activity via calcitonin receptor-mediated cAMP stimulation.
Main Results:
- Transgenic mice produced correctly processed hIAPP and mouse IAPP (mIAPP) with high bioactivity.
- Bioactive to immunoreactive ratios for hIAPP and mIAPP were 0.93 ± 0.18 and 1.19 ± 0.56, respectively.
- Plasma hIAPP was 4.6- to 7-fold more abundant than mIAPP in transgenic mice.
Conclusions:
- Transgenic mouse-produced hIAPP exhibits full biological activity.
- Validated transgenic mice as a model for in vivo hIAPP research.
- Supports further investigation into hIAPP's role in type 2 diabetes pathogenesis.