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Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Cutaneous expression of calcium/calmodulin-dependent protein kinase II in rats with type 1 and type 2 diabetes
Matija Boric1, Antonia Jelicic Kadic1, Livia Puljak1
1Laboratory for Pain Research, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
Abstract:
Changes in calcium-calmodulin protein kinase II (CaMKII) have been well demonstrated in nervous tissue of diabetic animal models. Skin shares the same ectodermal origin as nervous tissue and it is often affected in diabetic patients. The goal of this study was to analyze expression of CaMKII in rat foot pad 2 weeks and 2 months after induction of diabetes type 1 and 2. Forty-two Sprague-Dawley rats were used. Diabetes mellitus type 1 (DM1) was induced with intraperitoneally (i.p.) injected 55 mg/kg of streptozotocin (STZ) and diabetes mellitus type 2 (DM2) with a combination of high-fat diet (HFD) and i.p. injection of low-dose STZ (35 mg/kg). Two weeks and two months following diabetes induction rats were sacrificed and skin samples from plantar surface of the both hind paws were removed. Immunohistochemistry was performed for detection of total CaMKII (tCaMKII) and its alpha isoform (pCaMKIIα). For detection of intraepidermal nerve fibers polyclonal antiserum against protein gene product 9.5 (PGP 9.5) was used. The results showed that CaMKII was expressed in the skin of both diabetic models. Total CaMKII was uniformly distributed throughout the epidermis and pCaMKIIα was limited to stratum granulosum. The tCaMKII and pCaMKIIα were not expressed in intraepidermal nerve fibers. Two weeks after induction of diabetes in rats there were no significant differences in expression of tCaMKII and pCaMKIIα between DM1 and DM2 compared to respective controls. In the 2-month experiments, significant increase in epidermal expression of tCaMKII and pCaMKIIα was observed in DM1 animals compared to controls, but not in DM2 animals. This study is the first description of cutaneous CaMKII expression pattern in a diabetic model. CaMKII could play a role in transformation of skin layers and contribute to cutaneous diabetic changes. Further research on physiological role of CaMKII in skin and its role in cutaneous diabetic complications should be undertaken in order to elucidate its function in epidermis.
Insights
Calcium-calmodulin protein kinase II (CaMKII) expression increased in the skin of rats with type 1 diabetes after two months. This finding suggests CaMKII may contribute to skin changes in diabetes.
Area of Science:
- Biochemistry
- Dermatology
- Endocrinology
Background:
- Calcium-calmodulin protein kinase II (CaMKII) alterations are noted in nervous tissue of diabetic animal models.
- Skin, sharing ectodermal origins with nervous tissue, is frequently affected in diabetic patients.
Purpose of the Study:
- To investigate the expression patterns of CaMKII in rat skin following the induction of type 1 and type 2 diabetes.
- To analyze CaMKII expression at two weeks and two months post-diabetes induction.
Main Methods:
- Induction of type 1 diabetes (DM1) using streptozotocin (STZ) and type 2 diabetes (DM2) using a high-fat diet and low-dose STZ in Sprague-Dawley rats.
- Skin samples from the plantar surface of hind paws were collected at two weeks and two months.
- Immunohistochemistry was employed to detect total CaMKII (tCaMKII) and its alpha isoform (pCaMKIIα), with PGP 9.5 used for intraepidermal nerve fibers.
Main Results:
- CaMKII was expressed in the epidermis of both diabetic models, with tCaMKII uniformly distributed and pCaMKIIα localized to the stratum granulosum.
- No significant differences in tCaMKII and pCaMKIIα expression were observed at two weeks post-diabetes induction.
- A significant increase in epidermal tCaMKII and pCaMKIIα expression was noted in DM1 animals at two months, but not in DM2 animals.
Conclusions:
- This study provides the first description of cutaneous CaMKII expression in a diabetic model.
- CaMKII may play a role in skin layer transformation and contribute to diabetic cutaneous changes.
- Further research is warranted to elucidate the physiological role of CaMKII in skin and its involvement in diabetic complications.
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