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Regulation of vascular BK channels in diabetes by Nrf2 signaling
S90
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
Among them, GE is the most Significant one. The role of GE in the adolescent should not be overlooked. PC-12 Regulation of vascular BK channels in diabetes by Nrf2 signaling Hon-Chi LEE1 *, Yong LI1, Xiao-Li WANG1, Tong LU1. 1Mayo Clinic, United States of America Background and objective: The nuclear factor E2-related factor-2 (Nrf2) signaling pathway has emerged as a master regulator of cellular redox status. The large conductance calcium-activated potassium (BK) channels, which are major determinants of vasodilation, are impaired in diabetes mellitus (DM) due to the downregulation of BK-β1 by reactive oxygen species-dependent mechanisms. The goal of this study is to test the hypothesis that Nrf2 signaling plays a central role in the regulation of BK channel function in DM. Methods and results: Studies were performed combining cellular, molecular, vascular, and electrophysiological techniques. In type 2 diabetic db/db mouse aorta, Nrf2 protein expression was significantly reduced, associated with significant downregulation of BK-β1 and heme oxygenase 1 (HO-1), a known Nrf2 downstream target. Also, the muscle ring finger protein 1 (MuRF1), a known E-3 ligase targeting BK-β1, was significantly upregulated. These findings were reproduced by knockdown of Nrf2 by siRNA in cultured human coronary smooth muscle cells (HCSMC), whereas adenoviral transfer of Nrf2 gene in these cells was associated with downregulation of MuRF1 and upregulation of BK-β1 and HO-1 expression. Activation of Nrf2 by dimethyl fumarate in high glucose-cultured HCSMCs or in diabetic db/db mouse coronary arteries preserved BK-β1 expression shown by Western blot, BK channel activities using patch clamp recordings, and vascular function assessed by shear stress-mediated vasodilation in isolated mouse coronary arteries. Conclusions: Expression of BK-β1 is closely regulated by Nrf2 through its effect on MuRF1, which regulates BK-β1 degradation, and vascular BK channel function can be restored by activation of Nrf2. Nrf2 should be considered a novel therapeutic target in the treatment of diabetic vasculopathy. PC-13 Essential oil from sudachi peal improves glucose and lipid metabolism Keisuke FUKUTA1, Licht MIYAMOTO1 *, Rie TAKAHASHI1, Toshiaki TAMAKI2, Yasumasa IKEDA2, Koichiro TSUCHIYA1. 1 Dept. of Medical Pharmacology, Inst. of Biomedical Sciences, Tokushima University Graduate School, 2Dept. of Pharmacology, Inst. of Biomedical Sciences, Tokushima University Graduate School, Japan Background: According to the statement of the International Diabetes Federation, the diabetes population continues to grow around the world. The number of people associated with diabetes reaches 415 million in 2015, and one of 11 people is estimated to be a patient. It is predicted that it will increase to 642 million by 2040 if we do not take any effective measures. Recently, the alternative medicine such as supplemental foods and aromatherapy has attracted our attention. Among them, the mechanisms of the aromatherapy are still unknown for hypoglycemic effects. Sudachi is a citrus fruit grows in Tokushima prefecture region of Japan, and we found a suppressing effect on blood sugar level elevation by administration of its peel powder in human obese subjects. Because Sudachi has unique fragrance, we conducted a study to reveal the aromatic effects of essential oil from sudachi on the metabolic regulation. Method: These experiments were worked using male ddY mice. We exposed vaporized oil of sudachi peal to 7–8 weeks old mice for three weeks under the fixed concentration, then body weight, food intake and water intake were measured. The
intraperitoneal glucose tolerance test (IPGTT) was performed and the organ weight and plasma lipid levels were evaluated. We also analyzed expression levels of mRNA related to energy consumption. In addition, guanethidine was injected to another group to investigate involvement of the sympathetic nerve. Result: We found weight loss involving WAT reduction without change in food intake. Triglyceride (TG) in the blood was reduced by the treatment, and glucose tolerance was also improved. The expression of hepatic PGC-1 tended to be increased compared to control. When we administered guanethidine to the sudachi treated group, the reductions of plasma TG and WAT weight were canceled. These data suggest that vaporized sudachi oil may stimulate olfactory, resulting in the activation of the sympathetic nerve which participates in the reduction of WAT by facilitation of the energy consumption. PC-15 Construct an IDNT-NCP computer program for clinical management of patients with Diabetes Mellitus Wen-Ching TEH1, Te-Hsuan LIN1, Hsing-Yi WANG1, Hui-Chun HSU1, Ling-Wang AN2, Yu-Hung CHANG1, Der-Wei HWU1, Yau-Jiunn LEE1 *. 1Lee’s Endocrinology Clinic, Taiwan; 2Beijing Ruijing Diabetes Hospital, China Objective: Diabetic management model has been markedly changed over the past few decades especially on dietetic practice which have prompted dietitians to become more accountable and aware of treatment outcome and evaluation. Published evidence has demonstrated the numerous benefits which can be gained by application of a nutrition care process (NCP) and standardized language. However, a convenient, computerized, comprehensive tool to assess key NCP procedure is still lacking. Materials and methods: A Chinese version of computerized International Dietetics & Nutrition Terminology (IDNT) NCP program was constructed to assess diabetes nutrition behaviors. Results: The system is built using a Microsoft Solution based ASP.NET Web Site project template, SQL Server, and jQuery User Experience technique in rule engine. The trained Dietitians could be easily download automatically or enter patient’s basic personal, anthropometric data, physical exam findings, biochemical data, and food/nutrition history into the program to complete the nutritional assessment. After completeness of nutrition assessment, the program will make inference to the rule base and make nutrition diagnosis. Dietetics professionals could then make the final diagnosis decision for the patient based on the diagnosis report generated by the web based nutrition diagnosis expert system, which involves identifying and labeling nutrition-related problems, etiology, signs and symptoms statements for conditions. The system will also set up a window for the dietitians to implement the nutrition intervention, monitoring and evaluation plan, which involves formulating goals and determining plans of action and are integrated into overall disease management and implementation. The content validity index was calculated by experts’ ratings of item relevance. The ICVI was 0.7–1.0. To understand the interrater reliability of system, three groups including CDEs and 5 patients, involved the process of inter-rater reliability assessment to test the rating consistency among observational ratings is 95-0.98. Conclusion: A Chinese version of IDNT-NCP system build in a computer program may be a precise, convenient computerbased system to evaluate and follow the changes of eating behavior in patients with DM.
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
Among them, GE is the most Significant one. The role of GE in the adolescent should not be overlooked. PC-12 Regulation of vascular BK channels in diabetes by Nrf2 signaling Hon-Chi LEE1 *, Yong LI1, Xiao-Li WANG1, Tong LU1. 1Mayo Clinic, United States of America Background and objective: The nuclear factor E2-related factor-2 (Nrf2) signaling pathway has emerged as a master regulator of cellular redox status. The large conductance calcium-activated potassium (BK) channels, which are major determinants of vasodilation, are impaired in diabetes mellitus (DM) due to the downregulation of BK-β1 by reactive oxygen species-dependent mechanisms. The goal of this study is to test the hypothesis that Nrf2 signaling plays a central role in the regulation of BK channel function in DM. Methods and results: Studies were performed combining cellular, molecular, vascular, and electrophysiological techniques. In type 2 diabetic db/db mouse aorta, Nrf2 protein expression was significantly reduced, associated with significant downregulation of BK-β1 and heme oxygenase 1 (HO-1), a known Nrf2 downstream target. Also, the muscle ring finger protein 1 (MuRF1), a known E-3 ligase targeting BK-β1, was significantly upregulated. These findings were reproduced by knockdown of Nrf2 by siRNA in cultured human coronary smooth muscle cells (HCSMC), whereas adenoviral transfer of Nrf2 gene in these cells was associated with downregulation of MuRF1 and upregulation of BK-β1 and HO-1 expression. Activation of Nrf2 by dimethyl fumarate in high glucose-cultured HCSMCs or in diabetic db/db mouse coronary arteries preserved BK-β1 expression shown by Western blot, BK channel activities using patch clamp recordings, and vascular function assessed by shear stress-mediated vasodilation in isolated mouse coronary arteries. Conclusions: Expression of BK-β1 is closely regulated by Nrf2 through its effect on MuRF1, which regulates BK-β1 degradation, and vascular BK channel function can be restored by activation of Nrf2. Nrf2 should be considered a novel therapeutic target in the treatment of diabetic vasculopathy. PC-13 Essential oil from sudachi peal improves glucose and lipid metabolism Keisuke FUKUTA1, Licht MIYAMOTO1 *, Rie TAKAHASHI1, Toshiaki TAMAKI2, Yasumasa IKEDA2, Koichiro TSUCHIYA1. 1 Dept. of Medical Pharmacology, Inst. of Biomedical Sciences, Tokushima University Graduate School, 2Dept. of Pharmacology, Inst. of Biomedical Sciences, Tokushima University Graduate School, Japan Background: According to the statement of the International Diabetes Federation, the diabetes population continues to grow around the world. The number of people associated with diabetes reaches 415 million in 2015, and one of 11 people is estimated to be a patient. It is predicted that it will increase to 642 million by 2040 if we do not take any effective measures. Recently, the alternative medicine such as supplemental foods and aromatherapy has attracted our attention. Among them, the mechanisms of the aromatherapy are still unknown for hypoglycemic effects. Sudachi is a citrus fruit grows in Tokushima prefecture region of Japan, and we found a suppressing effect on blood sugar level elevation by administration of its peel powder in human obese subjects. Because Sudachi has unique fragrance, we conducted a study to reveal the aromatic effects of essential oil from sudachi on the metabolic regulation. Method: These experiments were worked using male ddY mice. We exposed vaporized oil of sudachi peal to 7–8 weeks old mice for three weeks under the fixed concentration, then body weight, food intake and water intake were measured. The
intraperitoneal glucose tolerance test (IPGTT) was performed and the organ weight and plasma lipid levels were evaluated. We also analyzed expression levels of mRNA related to energy consumption. In addition, guanethidine was injected to another group to investigate involvement of the sympathetic nerve. Result: We found weight loss involving WAT reduction without change in food intake. Triglyceride (TG) in the blood was reduced by the treatment, and glucose tolerance was also improved. The expression of hepatic PGC-1 tended to be increased compared to control. When we administered guanethidine to the sudachi treated group, the reductions of plasma TG and WAT weight were canceled. These data suggest that vaporized sudachi oil may stimulate olfactory, resulting in the activation of the sympathetic nerve which participates in the reduction of WAT by facilitation of the energy consumption. PC-15 Construct an IDNT-NCP computer program for clinical management of patients with Diabetes Mellitus Wen-Ching TEH1, Te-Hsuan LIN1, Hsing-Yi WANG1, Hui-Chun HSU1, Ling-Wang AN2, Yu-Hung CHANG1, Der-Wei HWU1, Yau-Jiunn LEE1 *. 1Lee’s Endocrinology Clinic, Taiwan; 2Beijing Ruijing Diabetes Hospital, China Objective: Diabetic management model has been markedly changed over the past few decades especially on dietetic practice which have prompted dietitians to become more accountable and aware of treatment outcome and evaluation. Published evidence has demonstrated the numerous benefits which can be gained by application of a nutrition care process (NCP) and standardized language. However, a convenient, computerized, comprehensive tool to assess key NCP procedure is still lacking. Materials and methods: A Chinese version of computerized International Dietetics & Nutrition Terminology (IDNT) NCP program was constructed to assess diabetes nutrition behaviors. Results: The system is built using a Microsoft Solution based ASP.NET Web Site project template, SQL Server, and jQuery User Experience technique in rule engine. The trained Dietitians could be easily download automatically or enter patient’s basic personal, anthropometric data, physical exam findings, biochemical data, and food/nutrition history into the program to complete the nutritional assessment. After completeness of nutrition assessment, the program will make inference to the rule base and make nutrition diagnosis. Dietetics professionals could then make the final diagnosis decision for the patient based on the diagnosis report generated by the web based nutrition diagnosis expert system, which involves identifying and labeling nutrition-related problems, etiology, signs and symptoms statements for conditions. The system will also set up a window for the dietitians to implement the nutrition intervention, monitoring and evaluation plan, which involves formulating goals and determining plans of action and are integrated into overall disease management and implementation. The content validity index was calculated by experts’ ratings of item relevance. The ICVI was 0.7–1.0. To understand the interrater reliability of system, three groups including CDEs and 5 patients, involved the process of inter-rater reliability assessment to test the rating consistency among observational ratings is 95-0.98. Conclusion: A Chinese version of IDNT-NCP system build in a computer program may be a precise, convenient computerbased system to evaluate and follow the changes of eating behavior in patients with DM.