• Food Science and Biotechnology
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• 제15권1호
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• pp.122-127
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• 2006

The effects of fermented chaga mushroom (Inonotus obliquus) powder on the lipid concentrations and the activities of liver marker enzymes of serum in genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats were investigated. Rats were fed a semisynthetic diet supplemented with 50 g/kg chaga mushroom powder (CM) or 50 g/kg fermented chaga mushroom powder (FCM) for 8 weeks (26 to 34 weeks of age). Nondiabetic Long-Evans Toknshima Otsuka (LETO) rats were used as age-matched nondiabetic control animals. Water consumption was significantly higher in the OLETF control than the LETO rats. Water consumption in the FCM-fed OLETF rats tended to be less than in both the OLETF control and CM-fed OLETF rats. Serum concentrations of triglycerides and total cholesterol were significantly higher in the OLETF control rats than in the LETO rats while within the OLETF rat groups, the consumption of FCM resulted in a significantly lower serum triglyceride concentration and slightly lowered serum total cholesterol concentration when compared to the OLETF control and CM-fed rats. The alanine aminotransferase (ALT) activity was significantly higher in the OLETF control than in the LETO rats, but this difference was significantly reduced compared to the CM-fed rats and essentially no difference in the ALT levels was observed between the LETO and OLETF-FCM rats. This observation suggests an adaptive effect of the fermented chaga mushroom in liver function. Livers of the LETO rats showed no histopathological changes, whereas those of the OLETF control rats were characterized by many fat depositions in the central zone of the hepatocytes. The livers of the OLETF CM-fed rats showed less fatty changes compared to the OLETF control rats and fat deposition in the hepatocytes was nearly absent. These results suggest that orally ingested fermented chaga mushroom has a potential beneficial effect on the complications known to occur in the obesity-related non-insulin dependent diabetes mellitus (NlDDM) OLETF rat.

• Food Science and Biotechnology
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• 제15권5호
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• pp.739-745
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• 2006

Changes in the levels of analytes in the blood and urine of a rodent animal model were taken as a measure of the hypoglycemic effects of a diet containing fermented chaga mushroom. These studies were conducted using the genetically manipulated diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The effects of 8-week long diets that included either fermented (FCM) or non-fermented (CM) chaga mushroom powder (5% in the diet) on the OLETF rat were compared to the normal diet fed OLETF rat and the non-diabetic Long-Evans Tokushima Otsuka (LETO) rat. Hypoglycemia was tracked by measuring serum and urine concentrations of glucose, insulin, fructosamine, and leptin. Serum and urine levels of glucose, fructosamine, and leptin in the OLETF rats were higher than in LETO rats when fed normal diets but insulin levels did not differ between the two animal groups. The FCM rats were characterized by dramatically low levels of serum glucose and leptin in the OLETF rats whereas the levels of fructosamine and urine glucose trended lower in response to FCM. The serum leptin level in the CM-fed OLETF rat was also lower than that in the normal diet fed OLETF control. Serum concentrations of insulin in the OLETF rats were higher following FCM or CM feeding compared to the normal diet. These observations imply that (a) a dietary supplement of fermented chaga mushroom may contribute to a hypoglycemic effect in the OLETF rat, and (b) the increased blood insulin concentration following 8 weeks of an FCM diet may be important to the noted improvement in hyperglycemia.

• The Korean Journal of Physiology and Pharmacology
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• 제14권2호
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• pp.99-103
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• 2010

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

• 대한임상검사과학회지
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• 제36권2호
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• pp.215-221
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• 2004

To determine the effects of caloric restriction on obese type 2 diabetes we measured body blood glucose and serum lipid level in dietary restricted Otsuka Long Evans Tokushima Fatty (OLETF) rats. OLETF rats (obese diabetic rats) and Long Evans Tokushima Otsuka (LETO) rats (control rats) were grouped into 2 groups; control (free feed) group and 30% caloric restricted (30% CR) group. At 24 weeks of age the 30% CR animals were provided a diet at a level of 30% less food (by weight) than control rats consumed during the previous week. Blood glucose levels and serum triglyceride, total cholesterol, and high density lipoprotein (HDL)-cholesterol levels of CR rats were determined every 2 weeks for 8 weeks total. Blood glucose, triglyceride and total cholesterol levels of OLETF rats were significantly higher compared to LETO rats. In OLETF rats, the blood glucose levels were decreased to 61% by 8 weeks in the 30% CR compared to the non-CR control group, but changes of blood glucose levels were not observed in LETO rats during the 8weeks in the 30% CR. The serum triglyceride levels of OLETF rats were decreased significantly in the 30% CR but no change in the serum of LETO rats was found. The total cholesterol level was not changed by dietary restriction in LETO rats, but significant changes were observed in OLETF rats by 30% dietary restriction. HDL-cholesterol levels were also increased by dietary restriction in both LETO and OLETF rats. These results suggested that elevated blood glucose, triglyceride and total cholesterol levels in diabetes II patients may be reduced by caloric restriction.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.850-857
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• 2001

The study was designed to observe whether the conjugated linoleic acid supplemented to diet could reduce plasma levels of glucose and lipids which were increased in 27-weeks old Otsuka Long Evans Tokushima Fatty(OLETF) rats. Twenty male OLETF rats of 7 weeks old were fed an experimental diet containing 4.5%(w/w) total fat including 1% CLA and six of twenty rats were sacrified at 6 weeks feeding. The rest of OLETF rats was divided into 2 groups, one group was continuously fed for 14 weeks more the same experimental diet containing 1% CLA and the other group was fed control diet which eliminated CLA. CLA did not significantly reduce food intake and body weight gain in OLETF obese rats. Plasma triglyceride and total cholesterol level were significantly increased at older age of OLETF obese rats, but CLA could significantly reduce plasma cholesterol and triglyceride increased in obese rats. However, CLA was not strong enough to reduce the increased plasma glucose level and hepatic lipogenic enzyme acitivies. CLA was mostly deposited in epididymal fat pad and could be incorporated into hepatic microsomal membrane and did interfere the conversion of C18 : 0 into C18 : 1 in liver. In conclusion, CLA could have anti-atherogenic effect by reducing plasma cholesterol and triglyceride which was increased in genetically obese rats, but CLA(1%) was not good source of dietary fatty acid to reduce body fatness and plasma glucose which was increased by obese gene in older rats.

• 대한수의학회지
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• 제54권1호
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• pp.21-26
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• 2014

Although benfotiamine has various beneficial anti-diabetic effects, the detailed mechanisms underlying the impact of this compound on the insulin signaling pathway are still unclear. In the present study, we evaluated the effects of benfotiamine on the hepatic insulin signaling pathway in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a type 2 diabetes mellitus model. OLETF rats treated with benfotiamine showed decreased body weight gain and reduced adipose tissue weight. In addition, blood glucose levels were lower in OLETF rats treated with benfotiamine. Following treatment with benfotiamine, the levels of Akt phosphorylation (S473/T308) in the OLETF groups increased significantly compared to the OLETF control group so that they were almost identical to the levels observed in the control group. Moreover, benfotiamine restored the phosphorylation levels of both glycogen synthase kinase (GSK)-$3{\alpha}/{\beta}$ (S21, S9) and glycogen synthase (GS; S641) in OLETF rats to nearly the same levels observed in the control group. Overall, these results suggest that benfotiamine can potentially attenuate type 2 diabetes mellitus in OLETF rats by restoring insulin sensitivity through upregulation of Akt phosphorylation and activation of two downstream signaling molecules, GSK-$3{\alpha}/{\beta}$ and GS, thereby reducing blood glucose levels through glycogen synthesis.

• 한국식품영양과학회지
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• 제30권6호
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• pp.1210-1214
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• 2001

본 실험은 식이 제한 급여에 따른 비만형 당뇨병 환자의 체중 및 혈중 지질량의 변화에 대한 연구의 일환으로 사람의 비만형 당뇨병과 유사한 병리소견을 나타내는 OLETF 횐쥐를 이용하여 자유급식군, 식이 급여량 20% 제한군과 식이 급여량 40% 제한군으로 나누어 12주간 사육한 후 체중과 혈당, 혈청 콜레스테롤 및 중성지질량을 측정하여 식이 제한 급여 에 따른 혈청 지질량의 변화를 관찰하였다. LETO 횐쥐에서 자유급식군은 12주 후 체중이 41% 증가되었으나 식이 급여량 20% 제한군은 22%, 식이 급여량 40% 제한군은 10%의 체중 증가를 나타냈고, OLETF 횐쥐에서 자유급식군은 24%, 식이 급여량 20% 제한군은 10%, 식이 급여량 40% 제한군은 -2%의 체중 증가를 나타냈다. 혈당량은 LETO 흰쥐에서 식이 급여량 20% 제한군은 혈당량이 감소되지 않았으나, 식이 급여량 40% 제한군은 12% 감소되고, OLETF 횐쥐 혈당량은 식이 급여량 20% 제한군은 15%, 식이 급여량 40% 제한군은 20%가 감소되었다. 혈청 중성지질량은 LETO흰쥐에서 식이 급여량 20% 제한군은 24%, 식이 급여량 40% 제한군은 27%가 감소되었고, OLETF 횐쥐에서는 식이 급여량 20% 제한군은 32%, 식이 급여량 40% 제한군은 37% 정도가 각각 감소되었다. 혈청 총 콜레스테롤량은 LETO 횐쥐에서는 자유급식군, 식이 급여량 20% 제한군과 식이 급여량 40% 제한군에서 모두 차이를 나타내지 않았고, OLETF 횐쥐에서는 식이 급여량 20% 제한군은 15%, 식이 급여량 40% 제한군은 23% 정도가 감소되었다. HDL-콜레스테롤량은 LETO 흰쥐에서 식이 급여량 20% 제한군은 34%, 식이 급여량 40% 제한군은 43%가 증가되었다. 이상의 실험결과로서 식이 제한 급여에 의한 체중, 혈당, 혈청 지질량의 변화가 OLETF 횐쥐에서 LETO 횐쥐에서 보다 더 유의한 것으로 나타나서, 식이 제한 급여에 의한 혈청 중성지질량과 혈청 총콜레스테롤 및 HDL-콜레스테롤량의 변화는 당뇨병에서 더 큰 변화가 유발되는 것으로 추측된다.

• 생명과학회지
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• 제22권5호
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• pp.634-641
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• 2012

LP9M80-H는 맥문동($Liriope$ $platyphylla$)으로부터 메탄올과 헥산을 이용하여 추출한 새로운 추출물로서 ICR 마우스에서 인슐린분비를 촉진하며, 간과 뇌 조직에서 인슐린 신호경로를 활성화시키는 것으로 알려져 있다. 본 연구에서는 LP9M80-H가 당뇨와 비만의 치료에 미치는 효과를 조사하기 위하여, OLETF 모델동물에 LP9M80-H를 2주간 투여한 후 당뇨와 비만과 관련된 주요인자의 변화를 관찰하였다. 비록 체중은 두 집단간에 차이가 없었으나 복부 지방량은 vehicle 투여군보다 LP9M80-H 투여군에서 적었다. 또한, 혈중 포도당농도는 LP9M80-H를 투여한 OLETF 랫드가 대조군에 비하여 약간 낮았으나 인슐린의 농도는 유의적으로 크게 증가하였다. 혈청 내 3가지 주요 지질의 농도는 LP9M80-H를 투여한 OLETF 랫드에서 유의적으로 감소하였고, 지방의 산화를 촉진하는 아디포넥틴의 농도도 LP9M80-H를 투여한 OLETF 랫드에서 감소하였다. 더불어, 체내에 분비된 인슐린이 표적장기에 미치는 영향을 관찰하기 위하여 간조직에서 인슐린 수용체와 인슐린 수용체기질(iRS)의 발현을 관찰하였으며, 이러한 2가지 단백질은 LP9M80-H를 투여한 OLETF 랫드에서 vehicle 투여군에 비해 유의미하게 감소하였다. 또한, 인슐린 신호 경로의 다운스트림에 위치하는 포도당 수송체 중에서 Glut-2와 Glut-3 발현은 LP9M80-H를 투여한 OLETF 랫드에서 유의미하게 감소하는 반면에, Glut-4 발현은 일정하게 유지되었다. 따라서 이러한 결과는 LP9M80-H는 포도당 항상성과 지질농도의 조절을 통하여 당뇨와 비만의 증상을 완화시키는데 기여할 것으로 사료된다.

• 한국식품영양과학회지
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• 제36권6호
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• pp.703-707
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• 2007

본 연구는 누에고치를 가수분해하여 얻은 실크단백질 효소 가수분해물이 비만형 당뇨병 모델인 OLETF 쥐의 당뇨병 개선에 미치는 영향을 조사하였다. 27주령의 OLETF 쥐를 당뇨대조군과 실크단백질 효소 가수분해물 0.5%, 0.8% 섭취군으로 나누어 19주 동안 음수로 섭취시켰다. 19주 동안 실험동물의 체중, 식이 섭취량, 음수 섭취량을 측정하고, 매주 2회씩 비공복과 공복 혈당변화를 관찰하였으며, 19주 후 모든 동물을 희생시킨 후 혈액을 채취하여 혈청지질과 인슐린 및 렙틴의 농도를 분석하였다. 당뇨대조군의 체중은 실크단백질 효소 가수분해물 섭취군에 비해 크게 감소하는 경향을 보였고, 총 콜레스테롤은 농도 의존적으로 그 수치가 낮아지는 경향을 보였으나 유의적 차이는 없었다. 또한 중성지질이나 HDL-cholesterol 함량 변화에도 큰 영향을 미치지 못하였다. 실크단백질 효소 가수분해물 섭취군은 대조군에 비하여 혈당 상승이 유의적으로 억제되었다. 17주 후 내당능 측정결과 실크단백질 효소 가수분해물 섭취군의 최고 혈당치가 농도 의존적으로 낮게 나타나는 경향을 보였으며 회복도 빨랐다. 인슐린과 렙틴은 농도 의존적으로 증가하였으며, 유의적인 차이를 보였다. 실크단백질 효소 가수분해물의 섭취는 인슐린과 렙틴의 대사에 관여하여 혈당상승을 억제하는 것으로 사료된다.

• 한국식품위생안전성학회지
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• 제28권2호
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• pp.152-157
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• 2013

본 연구는 동충하초(Isaria tenuipes)를 유전적 당뇨 질환 동물모델인 OLETF 랫드에서 4주간 경구 투여하여 항당뇨 효과에 대한 연구결과로써, OLETF 랫드 동충하초(Isaria tenuipes) 투여군은 당뇨대조군과 비교하여 투여 4주에는 사료 섭취량과 체중이 증가하였다. 이는 동충하초(Isaria tenuipes)를 섭취한 OLETF 랫드는 고지방식 사료만 섭취한 OLETF 랫드에 비해 당뇨 유발이 개선된 결과로 판단된다. 혈중 포도당 농도, 인슐린 농도 및 인슐린 저항성 지표인 HOMA-IR 수치가 용량 의존적으로 감소하였다. 또한 GLUT4 유전자 발현을 측정한 결과 대조군에 비해 동충하초(Isaria tenuipes) 투여군의 mRNA 및 단백질이 용량 의존적으로 증가하는 경향을 보였다. 따라서, 동충하초(Isaria tenuipes)의 섭취가 제2형 당뇨에서 인슐린의 감수성이나 저항성에 영향을 미치고, 혈당을 강화시키는 것으로 사료되므로 당뇨병환자의 혈당저하에 기여할 것이라 기대한다. 이에 본 연구는 천연물질을 이용한 당뇨병의 예방 및 치료에 동충하초(Isaria tenuipes)를 사용할 수 있는 이론적 토대를 제공할 것으로 생각된다.