－S 106 －
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Non-viral EGF (Epidermal Growth Factor) gene therapy accelerated cutaneous wound healing in streptozotocin diabetic C57BL/6J mice
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Paik Memorial Institute for Clinical Research, Pusan Paik Hospital, Inje University, Busan, Republic of Korea, 2Molecular Therapy Lab., Paik Memorial Institute for Clinical Research, 3Division of Endocrinology
and Metabolism, Department of Internal Medicine, Maryknoll General Hospital, Busan, Korea
*1,2Taekyoon Kim, 1,2Minjeong Kwon, 2Hyesook Chung, 2Changshin, Yoon 1,2Soonhee Lee
2,3Mikyung Kim, 1kyungsoo ko, 1Byungdoo Lee, 1,2Jeonghyun Park
Background: There are many kinds of growth factors in wound healing. EGF(Epidermal Growth Factor) is one of the important growth factors involved in wound healing. Although Topical peptide EGF has been used for the treatment of diabetic footulcer in the several countries, high cost, difficulty in tissue penetration and the inconvenience of daily application due to its short half life have limited its wide spread clinical usage. EGF gene therapy might have potential to overcome these limitations. Continuous production of EGF at the transfected tissue of the margin just beneath the skin wound might bypass the hostile degradation of EGF by over expressed proteinases, and the long term gene expression could enable so-called“one dose for cure". Material and Method: We divided mices into 3groups(Normal control, DM control and EGF(DM) injected group) and compared histopathology, wound size and EGF concentration. Streptozotocin was injected intraperitoneally to induce diabetes mellitus into C57BL/6J mice. To deliver of non-viral gene EGF828, Ultrasound micro-bubble destruction method with SonoVue(SF6) as a bubbling agent was used. And then, we observed tissue histopathology via H&E, Masson-trichrome and Immunohistochemistry(SMA, EGFR), wound size and measured Expressed EGF tissue concentrations via ELISA. Results: EGF expression concentration in EGF injected mice group was much higher on the 6th day and much lower on the 12th day of injection than normal and DM control mice group. Collagen production in EGF injected mice group was much higher than normal and DM control mice group, too. Histopathologic responses in EGF injected mice group were much improved comparing with DM control group. wound size in EGF injected mice group was much reduced on the 2nd and 4th day of injection. EGF enhances wound healing and blood flow at the early phase of wound healing in diabetic mice. EGF accelerated wound healing soundly in diabetic mice on histopathologic analysis. Conclusion: Non-viral EGF gene therapy could accelerate the cutaneous wound healing in stretpzotocin diabetic mice without any significant side effects. This strategy could be used in the actual human trial not only due to its superior efficacy but also appreciable safety.
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Relationship between hemoglobin A1c and lipid profile in type 2 diabetes patients with and without abdominal obesity
Department of Internal Medicine, Cheju National University School of Medicine1, Department of Internal Medicine, Konyang University College of Medicine2
*Seung Uk Jeong1, Keun-Yong Park2, Dong Mee Lim2, Gwan Pyo Koh1,
Background: Dyslipidemia is a common abnormality and important risk factor for cardiovascular diseases (CVD) in type 2 diabetes. Increased abdominal fat accumulation also influences cardiovascular disease and lipid parameters. This study was performed to analyze the relationship between hemoglobin A1c (A1C) and dyslipidemia in type 2 diabetes. Methods: This is cross-sectional study involving 283 type 2 diabetes patients from 2 different university hospitals. History and physical examination were done and fasting blood samples were taken for C-peptide and A1C, fasting glucose, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, apoB and apoAI. Patients were divided into abdominal and non-abdominal obesity groups depending on waist circumference (male 90cm, female 85cm). Results: Total cholesterol, triglyceride, LDL cholesterol and apoB were positively correlated with A1C in total subjects (r=0.252;P<0.001, r=0.154;P<0.01, r=0.223;P<0.001, r=0.205;P<0.01, respectively). In type 2 diabetes patients with abdominal obesity, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, apoB and apoAI were not correlated with A1C. In non-abdominal obesity group, however, total cholesterol, triglyceride, LDL cholesterol, apoB were positively related to A1C (r=0.371;p<0.001, r=0.217;p<0.01, r=0.309;p<0.001, r=0.260;p<0.01, respectively). On the multivariate analysis for type 2 diabetes patients without abdominal obesity, A1C contributed significantly to the variance in total (β=0.288, p<0.01) and LDL (β=0.339, p<0.001) cholesterols and apoB (β=0.307, p<0.01) after adjusting for age, sex, BMI, WC, smoking, duration of diabetes, C-peptide. Conclusions: Glycemic control is an important determinant of atherogenic lipoproteins in non-abdominal obesity group of type 2 diabetes patients. Therefore, it is suggested that strict glycemic control can reduce cardiovascular event due to dyslipidemia in this subgroup.
