Soon-Hee Lee

Increase of INS-1 cell apoptosis under glucose fluctuation and the involvement of FOXO-SIRT pathway

AIMS Variations of blood glucose level have been reported to be more harmful than sustained high glucose, but the effects on pancreatic β-cells have not yet been clarified. FOXO transcription factors are important for cell fate. We tried to clarify the effect of glucose variability on INS-1 cells, and the potential mechanisms related with FOXO-SIRT pathway. METHODS INS-1 cells were exposed to control, SHG (sustained high glucose) or IHG (intermittent high glucose) alternating every 12 h for 5 days. RESULTS INS-1 cells in SHG showed lower apoptosis and higher GSIS than IHG. Deacetylated FOXO and binding with SIRT were higher in SHG than IHG. Administration of PI3K inhibitor and/or SIRT inhibitor increased apoptosis and decreased Mn-SOD and Bcl-2 in SHG. CONCLUSIONS [corrected] IHG was more harmful to INS-1 cells than SHG. The degree of phosphorylation and acetylation of FOXO transcription factors were different between SHG and IHG, which might be one mechanism of increased INS-1 cell apoptosis in IHG.

Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice

Background To accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds. Methods Streptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF828 and VEGF165 DNAs. Each gene was modified for increasing efficacy as FRM-EGF828 or minicircle VEGF165. The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group. Results In both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant. Conclusion Both non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different.

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α‐glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily‐life treatment conditions in a large sample of Korean patients.

Viability of bone cement augmented compression hip screw system for the treatment of intertrochanteric fracture: a biomechanical analysis

Screw cut-out and non-union have been cited as major complications with hip screw systems for the treatment of intertrochanteric femoral fractures. Recently, cement augmentation of hip screw system has been introduced to provide better purchase of the screw. This study investigates the biomechanical efficacy of cement augmentation technique by assessing the changes in stress distributions within the femur and the surgical construct. Finite element models of the operated femur with sliding hip screw assemblies were constructed with and without bone cement augmentation. To simulate the fracture plane and other interfacial regions, 3-D contact elements were used with appropriate friction coefficients. Our results demonstrated the efficacy of the cement augmentation: 80% reduction in stresses was found in the cancellous bone due to cement augmentation, suggesting that the fractures of the cancellous bone and the cut-out of the screw are far less likely to take place. The peak von Mises stress within the cement mantle was about 1/3 of its fatigue strength. The likelihood of cement failure that might lead to osteolysis due to cement debris was not apparent. The micromotion at the hip screw interface was reduced from 0.275 mm to 0.008 mm, an indication for strong fixation after surgery.