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Updated: Aug 21, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Semicarbazide-sensitive amine oxidase in transgenic mice with diabetes
C Gokturk1, J Nordquist, H Sugimoto
1Section of Pharmacology, Department of Neuroscience, Uppsala University, Box 593, Biomedicum, 751 24 Uppsala, Sweden. camilla.gokturk@neuro.uu.se
Abstract:
Semicarbazide-sensitive amine oxidase (SSAO) activity in plasma is increased in diabetes, and in particular, in diabetic patients with vascular complications. It has been speculated that SSAO is involved in the development of such complications due to the production of cytotoxic compounds. In this work, we have induced diabetes in a previously described mouse-model, overexpressing SSAO in smooth muscle cells. SSAO activity was estimated as well as expression of the endogenous mouse gene and human transgene using real-time PCR. Diabetes induced an increase in SSAO activity in serum, kidney, and adipose tissue of transgenic animals. An inverse correlation between SSAO activity and mouse SSAO mRNA levels was observed in transgenic animals with diabetes. These results further support the suggestion of a negative feedback control of the SSAO gene expression. The increased SSAO activity in diabetes is most likely dependent on post-transcriptional modifications or activation of existing inactive enzyme molecules.
Insights
Diabetes increases semicarbazide-sensitive amine oxidase (SSAO) activity, likely via post-transcriptional modifications, not gene expression changes. This suggests a negative feedback loop in SSAO gene regulation during diabetes.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Semicarbazide-sensitive amine oxidase (SSAO) activity is elevated in diabetic patients, particularly those with vascular complications.
- SSAO is implicated in complication development through cytotoxic compound production.
- A mouse model overexpressing SSAO in smooth muscle cells was utilized.
Purpose of the Study:
- To investigate the impact of diabetes on SSAO activity and gene expression in a transgenic mouse model.
- To explore the relationship between SSAO activity and gene expression in diabetic conditions.
- To elucidate the regulatory mechanisms of SSAO expression in diabetes.
Main Methods:
- Diabetes was induced in SSAO-overexpressing transgenic mice.
- SSAO activity was measured in serum, kidney, and adipose tissue.
- Gene expression of mouse SSAO and human transgene was quantified using real-time PCR.
Main Results:
- Diabetes significantly increased SSAO activity in serum, kidney, and adipose tissue of transgenic mice.
- An inverse correlation was observed between SSAO activity and mouse SSAO mRNA levels in diabetic transgenic animals.
- These findings suggest a negative feedback mechanism regulating SSAO gene expression.
Conclusions:
- Increased SSAO activity in diabetes is likely due to post-transcriptional modifications or activation of existing enzyme molecules, rather than increased gene transcription.
- The results support the hypothesis of a negative feedback control on SSAO gene expression.
- Further research into post-transcriptional regulation of SSAO in diabetes is warranted.
