[논문]Streptozotocin 유도 당뇨병 생쥐 모델에서 지각 추출물의 항당뇨 효과

이경재; 임지성; 김지은; 이수경; 김현주; 송용선

doi:10.15188/kjopp.2023.02.37.1.1

Streptozotocin 유도 당뇨병 생쥐 모델에서 지각 추출물의 항당뇨 효과
Antidiabetic Effect of Aurantii Fructus Immaturus in Streptozotocin-induced Diabetes Model of Mice 원문보기

동의생리병리학회지 = Journal of physiology & pathology in Korean Medicine, v.37 no.1, 2023년, pp.1 - 8

이경재 (원광대학교 한의학전문대학원 제3의학과) , 임지성 (원광대학교 한의과대학 한방재활의학교실) , 김지은 (원광대학교 한의과대학 한방재활의학교실) , 이수경 (원광대학교 한의과대학 한방재활의학교실) , 김현주 (원광대학교 한의학전문대학원 제3의학과) , 송용선 (원광대학교 한의학전문대학원 제3의학과)

Abstract ▼ AI-Helper

The aim of this study is to evaluate the antidiabetic effect of the water extract of Aurantii fructus immaturus (WAF), in diabetic models using enzyme, cells and mice, and to suggest a putative mechanism explaining its antidiabetic effect. In an enzyme model using the enzyme α-glucosidase, WAF had no significant effect on α-glucosidase, as compared with acarbose, an antidiabetic drug. Nonetheless, WAF was capable of reducing the blood glucose levels during oral sucrose tolerance test and oral glucose tolerance test, implying that there would be other antidiabetic pathways in no relation to inhibition of α-glucosidase. In cell models using RIN-m5f β-cells and L6 myotubes, WAF, at its non-cytotoxic doses, augmented the secretion of insulin in RIN-m5f β-cells stimulated with 5 mM glucose. In addition, it enhanced the cellular uptake of glucose in L6 myotubes stimulated with deprivation of glucose for 12 h. Therefore, it is most likely that WAF may exert its antidiabetic effects, at least in part, by enhancing insulin secretion and glucose uptake. Meanwhile, in diabetic mice induced with peritoneal injection of streptozotocin (STZ), WAF significantly improved fast blood glucose levels, glycosylated hemoglobin levels, body weight loose, blood pressure, and diabetic adverse effects on functions of the kidney and the liver. Taken together, the water extract of Aurantii fructus immaturus may ameliorate diabetes in mice injected with STZ, at least in part, by enhancing insulin secretion and glucose uptake.

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표/그림 (16)

그림 Fig. 1. Effect of WAF on α-glucosidase activity. The antidiabetic drug acarbose was served as a positive control. Inhibitory activity of α -glucosidase was assayed by measuring the release of the product p-nitrophenol from the substrate p-nitrophenyl-α-D-glucopyranoside, as described in the section of Materials and Methods. Each point presents the mean ± SD of three independent experiments; ○ for acarbose and ● for WAF.
그림 Fig. 2. Effect of WAF on blood glucose levels in normal mice during OSTT. Acarbose was served as a positive control drug. Levels of blood glucose at indicated times were measured after oral treatment with WAF followed by oral treatment with sucrose (2 g/kg). OSTT was carried out as detailed in the section of Materials and Methods. Each value represents the mean ± SD (n = 6). *p < 0.05 compared with control group at the corresponding time; ● for control, ○ for 300 mg/kg acarbose, ■ for 100 mg/kg WAF, ▲ for 200 mg/kg WAF, ◆ for 400 mg/kg.
그림 Fig. 3. Effect of WAF on blood glucose levels in normal mice during OGTT. Metformin was served as a positive control drug. Levels of blood glucose at indicated times were measured after oral treatment with WAF followed by oral treatment with glucose (2 g/kg). OGTT was carried out as detailed in the section of Materials and Methods. Each value represents the mean ± SD (n = 6). *p < 0.05 compared with control group at the corresponding time; ● for control, ○ for 300 mg/kg acarbose, ■ for 100 mg/kg WAF, ▲ for 200 mg/kg WAF, ◆ for 400 mg/kg.
그림 Fig. 4. Effect of WAF on cell viability in RIN-m5F β-cells. Cells were exposed for 24 h to indicated concentrations of WAF. Cell viability was measured by MTT assay as detailed in the section of Materials and Methods. Each bar represents the mean ± SD (n = 6).
그림 Fig. 5. Effect of WAF on insulin secretion in RIN-m5F β-cells. Cells were exposed for 12 h with indicated doses of WAF, and then stimulated for 3 h with 15 mM glucose. Concentrations of insulin were determined by ELISA, as detailed in the section of Materials and Methods. Each bar represents the mean ± SD (n = 6). *p < 0.05 compared with the control, ^#p < 0.05 compared with the glucose alone.
그림 Fig. 6. Effect of WAF on cell viability in L6 myotubes. Cells were exposed for 24 h to indicated concentrations of WAF. Cell viability was measured by MTT assay as detailed in the section of Materials and Methods. Each bar represents the mean ± SD (n = 6).
그림 Fig. 7. Effect of WAF on cellular uptake of glucose-like 2-NBDG in L6 myotubes. L6 myobalsts were differentiated by 2% horse serum into L6 myotubes. Differentiated L6 myotubes were stimulated for 1 h with the positive control insulin (10 nM) or indicated doses of WAF, and 2-NBDG, then, was added for 30 min. The cellular uptake of 2-NBDG was measured, as detailed in the section of Materials and Methods. Each bar represents the mean ± SD (n = 6). *p < 0.05 compared with the control.
그림 Fig. 8. Effect of WAF on fasting blood glucose levels in diabetic mice. Diabetic mice were orally treated once a day with indicated doses of WAF for 4 weeks. Fasting blood glucose levels were measured weekly as detailed in the section of Materials and Methods. Each value represents the mean ± SD of 6 mice; ○ for normal mice, ● for diabetic mice, □ for diabetic mice treated with 200 mg/kg WAF, ■ for diabetic mice treated with 400 mg/kg. *p < 0.05 compared with the control group.
그림 Fig. 9. Effect of WAF on serum levels of glycosylated hemoglobin (HbA1c) in diabetic mice. Diabetic mice were orally treated once a day with indicated doses of WAF for 4 weeks. On day 28, serum HbA1c levels were measured as detailed in the section of Materials and Methods. Each bar represents the mean ± SD of 6 mice; 'Normal' for non-diabetic normal mice, 'Control' for diabetic mice treated with vehicle alone. *p < 0.05 compared with normal group, ^#p < 0.05 compared with control group.
그림 Fig. 10. Effect of WAF on serum levels of insulin in diabetic mice. Diabetic mice were orally treated once a day with indicated doses of WAF for 4 weeks. On day 28, serum insulin levels were measured as detailed in the section of Materials and Methods. Each bar represents the mean ± SD of 6 mice; 'Normal' for non-diabetic normal mice, 'Control' for diabetic mice treated with vehicle alone. *p < 0.05 compared with normal group, ^#p < 0.05 compared with control group.
그림 Fig. 11. Effect of WAF on body weight in diabetic mice. Diabetic mice were orally treated once a day with indicated doses of WAF for 4 weeks. Body weight was measured weekly as detailed in the section of Materials and Methods. Each value represents the mean ± SD of 6 mice; ○ for normal mice, ● for diabetic mice, □ for diabetic mice treated with 200 mg/kg WAF, ■ for diabetic mice treated with 400 mg/kg. *p < 0.05 compared with normal group, ^#p < 0.05 compared with control group.
그림 Fig. 12. Effect of WAF on systolic blood pressure in diabetic mice. Diabetic mice were orally treated once a day with indicated doses of WAF for 4 weeks. On day 28, systolic blood pressure was measured as detailed in the section of Materials and Methods. Each bar represents the mean ± SD of 6 mice; 'Normal' for non-diabetic normal mice, 'Control' for diabetic mice treated with vehicle alone. *p < 0.05 compared with normal group, ^#p < 0.05 compared with control group.
그림 Fig. 13. Representative photographs of kidney and liver obtained from normal and diabetic mice. Diabetic mice were orally treated once a day with indicated doses of WAF for 4 weeks. One of 6 photographs is representatively illustrated.
표 Table 1. Effect of WAF on weight of kidney and liver in normal and diabetic mice
표 Table 2. Effect of WAF on serum BUN and creatinine in normal and diabetic mice
표 Table 3. Effect of WAF on serum GOT and GPT in normal and diabetic mice

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