Cutaneous expression of calcium/calmodulin-dependent protein kinase II in rats with type 1 and type 2 diabetes

• tCaMKII was expressed throughout all the layers of epidermis.
• pCaMKIIα expression was restricted to the stratum granulosum of epidermis.
• tCaMKII and pCaMKIIα were not present in intraepidermal nerve fibers.
• tCaMKII and pCaMKIIα increased in DM1 animals 2 months after induction of diabetes.

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.