• Food Science and Biotechnology
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• v.15 no.1
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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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• v.15 no.5
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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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• v.14 no.2
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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.

• Korean Journal of Clinical Laboratory Science
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• v.36 no.2
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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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• v.34 no.8
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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.

• Korean Journal of Veterinary Research
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• v.54 no.1
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.6
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• pp.1210-1214
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• 2001

To determine the effects of dietary restriction on obese type 2 diabetes we measured body weight, blood glucose and serum lipid level in dietary restricted Otsuka Long Evans Tokushima Fatty (OLETF) rats. OLETF rats (obese diabetic rats) and LETO rats (control rats) were grouped into 3 groups; control (free feed) group, 20% dietary restricted (20% DR) group and 40% dietary restricted (40% DR) group. Body weight of rats was measured every weeks and the level of glucose, triglyceride (TG), total cholesterol (TC) and HDL-cholesterol in blood of rats were also determined at 12 weeks after dietary restriction. Body weight of control, 20% DR and 40% DR groups were increased by 41%, 20% and 10%, respectively in LETO rats and by 24%, 10% and -2%, respectively in OLETF rats. Blood glucose level of LETO rats were decreased by 12% on 40% DR compared to control group but the differences between control group and 20% DR group was not observed. The blood glucose level of OLETF rats were decreased by 20% in 40% DR group and by 15% in 20% DR group. The levels of blood triglyceride in 20% DR and 40% DR group were decreased by 20%, 15% in LETO rats and by 37%, 32% in OLETF rats, respectively Total cholesterol revel was not changed by dietary restriction in LETO rats, but significant changes were observed in OLETF rats by both 20% and 40% dietary restriction. HDL-cholesterol levels were also increased by dietary restriction in both LETO and OLETF rats. These results suggested that body weight and blood glucose, serum triglyceride and total cholesterol levels were decreased by dietary restriction and these changes are more susceptive in diabetic rats than non-diabetic animals.

• Journal of Life Science
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• v.22 no.5
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• pp.634-641
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• 2012

It was reported that the novel compounds (LP9M80-H) of $Liriope$ $platyphylla$ regulate glucose transporter (Glut) biosynthesis by activating the insulin-signaling pathway in the liver and brain of ICR mice. To investigate the therapeutic effects of LP9M80-H on the pathology of diabetes and obesity, alterations of key factors related to symptoms were analyzed in the Otsuka Long Evans Tokushima Fatty (OLETF) rats treated with LP9M80-H for 2 weeks. The abdominal fat masses in the LP9M80-H-treated group were lower than the vehicle-treated group, although there was no difference in body weight between the two groups. Additionally, when compared to the vehicle-treated group, LP9M80-H treatment induced a significant decrease in glucose levels and an increase in the insulin concentration in the blood of OLETF rats. A high level of insulin protein was also detected in pancreatic ${\beta}$ cells of LP9M80-H-treated OLETF rats. A significant reduction in the concentration of lipids and adiponectin was detected only in LP9M80-H-treated OLETF rats. Furthermore, the expression of insulin receptor ${\beta}$ and the insulin receptor substrate (IRS) was dramatically decreased in LP9M80-H-treated OLETF rats compared to the vehicle-treated group. Of the glucose transporters located downstream of the insulin-signaling pathway, glucose transporters (Glut) -2 and -3 were significantly decreased in LP9M80-H-treated OLETF rats, while the level of Glut-4 was maintained under all conditions. Therefore, these results suggest that LP9M80-H may contribute to relieving symptoms of diabetes and obesity through glucose homeostasis and regulation of lipid concentration.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.6
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• pp.703-707
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• 2007

This study was performed to investigate the effect of silk protein hydrolysates hydrolyzed by protease on blood glucose level, serum insulin and leptin secretion in the OLETF rats. Twenty seven week-old-male OLETF rats were divided in three groups: diabetic control, 0.5% and 0.8% silk protein hydrolysates groups that were fed daily for 19 weeks. Body weight increased in the 0.5% and 0.8% silk protein hydrolysates fed groups compared with diabetic control group. Food and water intake were not different among diabetic and silk protein hydrolysates groups. In random state, the blood glucose levels in silk protein hydrolysates fed groups were lower than diabetic control group; however, the blood glucose in the three groups were not different in fasting state. Also silk protein hydrolysates improved the glucose tolerance in OLETF rat. The silk protein hydrolysates did not influence serum lipids while serum insulin and leptin levels were increased in the experimental OLETF rats. These results suggested that the administration of silk protein hydrolysates solution reduced significantly (p<0.05) an increasing rate of blood glucose level by stimulating the insulin secretion and increasing the serum leptin level.

• Journal of Food Hygiene and Safety
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• v.28 no.2
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• pp.152-157
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• 2013

We evaluated the anti-diabetic effects of Isaria tenuipes in diabetes mellitus type 2. For the experiments, the diabetic animal model OLETF rats were divided to 4 groups: Isaria tenuipes was administered mixed with the high fat diet 45% at dose levels of 0.0%, 0.1%, 1.0%, and 5.0% for 4 weeks. All animals have free access to water and high fat diet 45%. The diabetic clinical markers, including clinical signs, body weight and food intake, organ weights, blood glucose level, insulin level and HOMA-IR index, oral glucose tolerance test, GLUT4 mRNA and protein were measured at a time. After administration for 4 weeks, the blood glucose levels, insulin levels and HOMA-IR index of test groups were decreased compared with control group in dose-dependent manner. The body weight and diet consumptions were reduced in control group at 4 weeks. The treatments of Isaria tenuipes also showed high expression of GLUT4 mRNA and protein in the muscle of OLETF rats. The results suggest that Isaria tenuipes has anti-hyperglycemic effect attenuating blood glucose in the animal model of type 2 diabetes and might be useful as a functional diet for human diabetic diseases.