Characteristics of the Epidermis and Stratum Corneum of Hairless Mice with Experimentally Induced Diabetes Mellitus

Abstract

Diabetes mellitus induces many pathophysiologic changes in the skin. Even so, dermatologists still lack an animal model of diabetes that enables the direct evaluation of the various functional properties of the skin. Our group induced two types of an experimental type 1 diabetes model in hairless mice by administering either streptozotocin or alloxan, in order to examine the properties of the stratum corneum and epidermis of these animals. The plasma glucose concentrations of the mice at 3 wk after their i.v. injection were significantly higher than those of control mice (streptozotocin, 3.2-fold; alloxan, 3.7-fold). The stratum corneum water content was significantly reduced in both types of diabetic mice, whereas the transepidermal water loss remained unchanged. The amino acid content with normal epidermal profilaggrin processing was either normal or elevated in the stratum corneum of the streptozotocin-treated mice. In contrast, the stratum corneum triglyceride content in the streptozotocin-treated mice was significantly lower than the control level, even though the levels of ceramides, cholesterols, and fatty acids in the stratum corneum were all higher than the control levels. The streptozotocin-treated group also exhibited decreases in basal cell proliferation and epidermal DNA content linked with an increase in the number of corneocyte layers in the stratum corneum, suggesting that the rates of epidermal and stratum corneum turnover were slower in the streptozotocin-treated animals than in the normal controls. In contrast, there were no remarkable changes in any of the epidermal differentiation marker proteins examined. This finding in diabetic mice, namely, reduction in both the epidermal proliferation and stratum corneum water content without any accompanying impairment in the stratum corneum barrier function, is similar to that found in aged human skin. Our new animal model of diabetes will be useful for the study of diabetic dermopathy as well as the mechanisms of stratum corneum moisturization.

Optical and structural properties of biological tissues under diabetes mellitus

“…Contradicting results were also obtained in the studies of epidermis thickness in the case of diabetes [57]. In some papers the authors conclude that the epidermis thickness does not change [170,172,173] under the conditions of long-term hyperglycemia in rats and the diabetes mellitus in humans and mice, however, other authors using other model of diabetes mellitus or animals of other age state that the thickness either decreases [171,172,174], or increases [175]. The ultrasonic measurement of skin thickness in patients with diabetes mellitus revealed the skin thickness increase [176].…”

“…However, in Refs. [169,171] it was stated that in the case of diabetes mellitus the transepidermal loss of water does not increase. The authors of Ref.…”

“…In mice with model diabetes mellitus, the reduction of keratinocyte proliferation in epidermis was observed [57, 171,172], while in Refs. [170,172] no such changes were observed in the experiments with rats and mice of other age.…”

Up-regulation of Loricrin Expression by Cell Adhesion Molecule Nectin-1 through Rap1-ERK Signaling in Keratinocytes

“…Immunoblot Analysis-As described previously (30), the epidermis was homogenized in a lysis buffer (0.1 M Tris hydroxymethyl aminomethan-HCl (pH 9.0), 8 M urea, 1% 2-mercaptoethanol, 1% SDS, 1 mM EDTA, and 0.1 mM phenylmethylsulfonyl fluoride) and centrifuged (15,000 ϫ g for 15 min). The supernatant was used for immunoblotting.…”

The percutaneous permeability and absorption of dexamethasone esters in diabetic rats: a preliminary study

“…Sakai et al reported that the SC hydration and the activity of sebaceous glands decreased obviously in diabetics (Sakai et al, 2005). There were also studies that indicated hyperglycemia and decreased insulin signal were involved in the impairment of skin function (Sakai et al, 2003;Seirafi et al, 2008). In the presence of high glucose (20 mmol/l), the keratinocytes was larger, flattened and had lost some of their orientation toward each other, and the keratinocytes proliferation was decreased.…”