[논문]C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과

김선영; 박재은; 한지숙

doi:10.5352/jls.2019.29.5.570

C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과
Tenebrio molitor (Mealworm) Extract Improves Insulin Sensitivity and Alleviates Hyperglycemia in C57BL/Ksj-db/db Mice 원문보기

생명과학회지 = Journal of life science, v.29 no.5 = no.229, 2019년, pp.570 - 579

김선영 (부산대학교 식품영양학과) , 박재은 (부산대학교 식품영양학과) , 한지숙 (부산대학교 식품영양학과)

초록
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당뇨병은 서구화된 식습관으로 발생하는 심각한 만성대사질환의 하나이며, 당뇨병의 치료는 혈당을 정상적인 수준으로 유지하며 당뇨 합병증을 예방하는 것이다. 따라서 본 연구는 당뇨병 및 인슐린 저항성에 대한 유전적 분석에 널리 이용되는 C57BL/Ksj-db/db 당뇨동물모델을 이용하여 갈색거저리 유충(밀웜) 추출물의 6주간 섭취가 혈당개선에 미치는 영향에 대해 조사하고 이에 인슐린 민감성 개선과 당대사 조절을 통한 항당뇨 효과를 규명하고자 하였다. 제 2형 당뇨동물모델 실험 결과, db/db-MWE군(식이 0.5%)이 db/db-control군에 비해 유의적(p<0.05)으로 혈당이 감소하였다. 약물군인 db/db-RG군(식이 0.05%)은 부작용에 의해 눈에 띄게 체중이 증가하였으나, db/db-MWE군에서는 약물군에서의 체중증가와 같은 큰 부작용 없이 혈당 감소효과를 나타내었다. HbA1c와 혈장인슐린 농도의 경우 db/db-control군에 비해 db/db-MWE군이 유의적(p<0.05)으로 낮았다. 또한 골격근에서 p-IRS, p-AKT, PM-GLUT4의 발현을 확인한 결과, db/db-MWE군에서 db/db-control군에 비해 p-IRS, p-AKT, PM-GLUT4의 발현이 증가된 것을 알 수 있었다. 이는 밀웜 추출물의 섭취가 골격근 내로 당이 원활이 유입되도록 도와주어 인슐린 민감성을 개선시키며, 고혈당 증상을 개선시킨 것으로 사료된다. 밀웜 추출물을 식이에 0.5% 첨가하여 6주간 C57BL/Ksj-db/db 당뇨동물모델에 제공한 결과, 공복혈당과 HbA1c의 감소 및 인슐린 저항성을 개선시켰다. 이는 인슐린 민감성을 증가시키고, 당 대사 조절을 통해 고혈당 증상의 완화에 기인한 것으로 보인다. 따라서 밀웜은 당뇨병의 예방과 치료에 유용한 소재가 될 것으로 기대되며, 향후 제 2형 당뇨병 개선을 위해 더욱 다양한 연구가 이루어져야 할 것으로 사료된다.

Abstract ▼ AI-Helper

Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

주제어

표/그림 (8)

표 Table 1. Ingredient composition of the experimental diets supplemented to mice
그림 Fig. 1. Weekly changes in body weight in C57BL/KsJdb/db mice supplemented with mealworm extract.
그림 Fig. 2. Weekly changes in blood glucose levels in C57BL/KsJ-db/db mice supplemented with mealworm extract.
표 Table 2. The effects of supplmentation with MWE on food consumption and drinking water intake of C57BL/KsJdb/db mice
그림 Fig. 3. The effects of supplmentation with MWE on blood glycosylated hemoglobin levels and markers of insulin resistance in C57BL/KsJ-db/db mice.
그림 Fig. 4. The effects of supplementation with MWE on intraperitoneal glucose tolerance tests in C57 BL/KsJ- db/db mice.
그림 Fig. 5. The effect of MWE supplementation on pIRS-1, IRS-1, PI3K, pAkt, and Akt protein expression in skeletal muscle of C57BL/KsJ-db/db mice.
그림 Fig. 6. The effect of MWE supplementation on PM-GLUT4 and GLUT4 protein expression in skeletal muscle of C57BL/KsJ-db/db mice.

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제안 방법

molitor have been used in traditional medicine to curb hepatofibrosis and diabetes [32]; however, no study has investigated the use of a mealworm to improve insulin sensitivity in type 2 diabetic mice. Therefore, we designed this study to examine the efficacy of the mealworm extract (MWE) on insulin sensitivity and hyperglycemia in C57BL/Ksj-db/db type 2 diabetic mice.
To clarify whether MWE supplement promotes the activation of insulin signaling pathway and leads to glucose uptake into cells of skeletal muscles, activation of PI3K/Akt pathway was investigated by observing the phosphorylation levels of IRS-1 and Akt, and by activation of PI3K. As presented in Fig.

대상 데이터

The blocked membranes were incubated with respective antibodies overnight at 4℃. Antibodies against IRS-1, PI3K, phospho-Akt^Ser473, Akt, and GLUT4 were purchased from Abcam (Cambridge, UK). Antibodies against phospho-IRS-1^Tyr612 were purchased from Thermo Fisher Scientific (Rockford, IL, USA).
Mealworm was purchased from Yongin (Yongin, Gyeonggi-do, Korea). It was washed with distilled water, and then dried and ground into a powder (Shinhan Science & Technology Co.

데이터처리

Differences between the groups were evaluated for significance using one-way analysis of variance (ANOVA) followed by Duncan’s multiple range post-hoc tests.

성능/효과

65%[30]. According to these results, omega-3 fatty acids or chitin and chitosan in MWE may contribute, at least in part, to stimulate insulin signaling pathway in the db/db mice.
Consequently, at the end of the experiment, fasting blood glucose was 525.63±57.4 and 269.50±87.47 in the db/db-control and db/db-MWE groups, respectively, that is, the fasting blood glucose level of mice in the db/db-control group was twice higher than that observed in the db/db-MWE group.
2 presents the effect of MWE supplement on fasting blood glucose levels. During the commencement of the experiment, blood glucose levels did not significantly differ among the groups; however, fasting blood glucose levels of mice in db/db-control group were elevated throughout the experiment, presumably indicating the disease progression, whereas fasting blood glucose levels of mice in db/db-MWE group were slightly increased. Consequently, at the end of the experiment, fasting blood glucose was 525.
In conclusion, MWE supplementation effectively decreased hyperglycemia in type 2 diabetic db/db-mice. This was because MWE enhanced insulin sensitivity via activation of PI3K/Akt pathway, increased GLUT4 translocation in plasma membrane, and facilitated glucose uptake in the skeletal muscle cells.
HOMA-IR is homeostatic index of insulin resistance, which is decreased with increasing insulin sensitivity. In this study, HOMA-IR was significantly lower in mice of db/db-MWE group than those of the db/db-control group. These observations imply that MWE supplementation might contribute in improving insulin resistance.
As a result, GLUT4 is transferred to the plasma membrane to absorb blood glucose into the cell [3, 11, 34]. In this study, the supplementation of mealworm extracts significantly increased the levels of gene expression in insulin signaling pathway. MWE significantly increased phosphorylation of IRS-1^Tyr612 and Akt^Ser473, and activation of PI3K in skeletal muscles.
This was because MWE enhanced insulin sensitivity via activation of PI3K/Akt pathway, increased GLUT4 translocation in plasma membrane, and facilitated glucose uptake in the skeletal muscle cells. Therefore, this study suggests that MWE can possess a potential for improving insulin sensitivity and alleviating hyperglycemia via insulin signaling pathway in skeletal muscles of db/db-mice.
01 in the db/db-control and db/db-MWE groups, respectively. This indicated that the HbA1c levels, plasma insulin levels, and HOMA-IR values in the db/db-MWE group were significantly lower compared with those in the db/db-control group.
Intraperitoneal glucose tolerance test was performed to assess the insulin sensitivity and utilization of excessive blood glucose [1, 21]. This study demonstrated that blood glucose levels were restored to levels close to the basal value after 120 min of glucose injection in db/db-MWE and db/db-RG groups compared with the db/db-control group. According to this result, supplementation of MWE increases the insulin sensitivity and effectively controls the blood glucose concentrations.

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