ABSTRACT
Type 2 diabetes is a lifestyle-related disease that affects people worldwide and is especially prevalent in the elderly. Many elderly people with diabetes also complain of dry skin; however, the relationship between aging and dry skin in type 2 diabetes is unknown. The purpose of this study was to examine the interaction between aging and dry skin using the specific pathogen-free KK-Ay/TaJcl type 2 diabetes mouse model. Skin dryness in this model increases with age and was evaluated at 10, 27, 40, and 50 weeks. We observed increased mast cell expression, increased histamine and matrix metalloproteinase-1 levels, and decreased collagen expression in the skin of aging KK-Ay/TaJcl mice. In addition, the increased expression of angiopoietin 2, interleukin-6, tumor necrosis factor-α, and endostatin in the blood indicated kidney damage in this model. Aging KK-Ay/TaJcl mice also showed fatty liver pathology, which led to increased reactive oxygen species in the blood and liver, as well as the increased expression of M1 macrophages in the liver. These results showed that dry skin is associated with skin, kidney, and liver interactions in an aging type 2 diabetes mouse model.
ABSTRACT
Various diabetic drugs have been developed as the number of patients with type 2 diabetes has increased. Sodium-glucose cotransporter (SGLT)-2 inhibitors have been developed as novel therapeutic agents. However, SGLT-2 inhibitors cause skin dryness. The mechanism through which SGLT-2 inhibitors cause skin dryness is unknown. The purpose of this study was to investigate the mechanism through which dapagliflozin, a SGLT-2 inhibitor, induces skin dryness. Specific pathogen-free KK-Ay/TaJcl (type 2 diabetes model) mice were orally administered with SGLT-2 inhibitor (dapagliflozin) daily for 4 weeks at a dose of 1 mg/kg/d. Skin dryness induced in KK-Ay/TaJcl mice became severe after dapagliflozin administration. Dapagliflozin treatment decreased collagen type I and hyaluronic acid levels in mice; additionally, it affected the transforming growth factor (TGF)-ß/hyaluronan synthase pathway, further reducing hyaluronic acid levels. The results indicate that the reduction in hyaluronic acid levels plays an important role in the occurrence of dry skin in diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Sodium-Glucose Transporter 2 Inhibitors , Animals , Benzhydryl Compounds/pharmacology , Benzhydryl Compounds/therapeutic use , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Disease Models, Animal , Glucosides , Hyaluronic Acid , Hypoglycemic Agents/therapeutic use , Mice , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
Diabetes induces dry skin that may cause infective diseases. In this study, we aimed to clarify the mechanism of diabetes-induced skin dryness in animal models. We also examined the difference in the mechanism of skin dryness in type 1 and type 2 diabetes. We examined skin dryness in type 1 diabetes model mice (streptozotocin [STZ] induction), non-obesity type 2 diabetes model mice (newborn STZ injection), and obesity type 2 diabetes model mice (KK-Ay/TaJcl). An increase in transepidermal water loss was observed in the type 1 diabetes model mice, and reduced skin hydration was observed in the type 2 diabetes model mice. In the type 1 diabetes model mice, an increase in advanced glycation end products and matrix metalloproteinase-9 led to a decline in collagen IV level, inducing skin dryness. In the obesity type 2 diabetes model mice, an increase in the release of histamine and hyaluronidase by mast cells resulted in a decline in the level of hyaluronic acid, inducing skin dryness. However, in the non-obesity type 2 diabetes model mice, the main factors of skin dryness could not be clearly identified. Nevertheless, inflammatory cytokine levels increased. We hypothesize that inflammatory cytokines disrupt the collagen of the skin. Diabetes caused skin dryness in each mouse model, and the mechanism of skin dryness differed by diabetes type.
Subject(s)
Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Skin Diseases/etiology , Skin/pathology , Animals , Collagen Type IV/analysis , Collagen Type IV/metabolism , Cytokines/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Type 1/chemically induced , Diabetes Mellitus, Type 2/chemically induced , Disease Models, Animal , Glycation End Products, Advanced/metabolism , Humans , Male , Matrix Metalloproteinase 9 , Mice , Signal Transduction/immunology , Skin/chemistry , Skin/immunology , Skin Diseases/pathology , Streptozocin/administration & dosage , Streptozocin/toxicityABSTRACT
Pharmacists were officially recognized as essential supporters of medical treatment by the Japanese Ministry of Public Welfare in 1992. However, most pharmacists in Japan do not yet play a sufficient role in their duties. Reasons for the above situation include a lack of social understanding regarding their duties and responsibility for the clinical treatment of patients and a lack of awareness on ensuring safe drug therapy by accepting medication errors in prescription, dispensing and administration. No guidelines to minimize these errors have been initiated either. The School of Pharmacy, Department of Pharmacology thus introduced a six-year program to address these problems in April, 2006 in Japan. Accordingly the pharmacist is required to play a bigger role in pharmaceutical treatment in the clinical arena. We must provide the highest level of pharmaceutical care possible to patients, medical, nursing and other hospital personnel and develop pharmaceutical students in the clinical arena. Here, I describe the clinical education trial for pharmaceutical students in Saiseikai Matsusaka Hospital.
