• 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.

• 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.

• 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.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.181-186
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• 2012

Fenofibrate is a selective peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) activator and is prescribed to treat hyperlipidemia. The mechanism through which $PPAR{\alpha}$ agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.1
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• pp.7-12
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• 2008

OLETF (Otsuka Long-Evans Tokushima Fatty) rats are characterized by obesity-related insulin resistance, which is a phenotype of type 2 diabetes. Sulfonylurea drugs or benzoic acid derivatives as inhibitors of the ATP-sensitive potassium $(K_{ATP})$ channel are commercially available to treat diabetes. The present study compared sulfonylurea drugs (glimepiride and gliclazide) with one of benzoic acid derivatives (repaglinide) in regard to their long-term effect on ameliorating insulin sensitivity in OLETF rats. Each drug was dissolved and fed with drinking water from 29 weeks of age. On high glucose loading at 45 weeks of age, response of blood glucose recovery was the greatest in the group treated with glimepiride. On immunohistochemistry analysis for the Kir6.2 subunit of $K_{ATP}$ channels, insulin receptor ${\beta}$-subunits, and glucose transporters (GLUT) type 2 and 4 in liver, fat and skeletal muscle tissues, the sulfonylurea drugs (glimepiride and gliclazide) were more effective than repaglinide in recovery from their decreased expressions in OLETF rats. From these results, it seems to be plausible that $K_{ATP}$-channel inhibitors containing sulfonylurea moiety may be much more effective in reducing insulin resistance than those with benzoic acid moiety. In contrast to gliclazide, non-tissue selectivity of glimepiride on $K_{ATP}$ channel inhibition may further strengthen an amelioration of insulin sensitivity unless considering other side effects.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.1
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• pp.31-36
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• 2007

To elucidate a potential molecular link between diabetes and atherosclerosis, we investigated the role of Janus tyrosine kinase(JAK) for NAD(P)H oxidase-derived superoxide generation in the enhanced proliferative capacity of vascular smooth muscle cells(VSMC) of Otsuka Long-Evans Tokushima Fatty(OLETF) rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum(FBS) and superoxide generation with an increased NAD(P)H oxidase activity were observed in diabetic(OLETF) VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated by AG490, JAK2 inhibitor, and PP2, Src kinase inhibitor. Tyrosine phosphorylation of proteins in diabetic VSMC, especially JAK2, was increased compared to control VSMC. Furthermore, the enhanced NAD(P)H oxidase activity in diabetic VSMC was significantly attenuated by AG490 in a dose-dependent manner. Together, these results indicate that the signal pathway which leads to diabetes-associated activation of Src kinase/JAK is critically involved in the diabetic VSMC proliferation through NAD(P)H oxidase activation and superoxide generation.