• Journal of Ginseng Research
• /
• v.41 no.4
• /
• pp.503-512
• /
• 2017

Background: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. Methods: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). Results: The weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

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

• BMB Reports
• /
• v.35 no.5
• /
• pp.494-497
• /
• 2002

The present study explored the short-term effects of dietary conjugated-linoleic acid (CLA) on liver lipid metabolism in starved/refed Otsuka Long Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (12 weeks old) were starved for 24 hours, then refed for 48 hours with either a CLA diet [7.5% CLA and 7.5% Safflower oil (SAF)] or a SAF control diet (15% SAF). The results demonstrated a 30% reduction of hepatic triglyceride (TG) concentration in the CLA group when compared to the control group. Liver cholesterol concentration was also 26% lower in the CLA fed rats. The activity of mitochondrial carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, was moderately elevated by 1.2-fold in the livers of the CLA group when compared to the control. In contrast, phosphatidate phosphohydrolase, the rate-limiting enzyme for TG synthesis, was found to be 20% lower in the livers of the CLA-fed rats. Therefore, dietary CLA evidently lowers liver lipid concentrations through a reduced TG synthesis and enhanced fatty acid oxidation in starved/refed OLETF rats.

• Biomedical Science Letters
• /
• v.17 no.4
• /
• pp.273-281
• /
• 2011

Our previous study demonstrated that the Korean traditional medicine Gyeongshingangjeehwan (GGEx) inhibits obesity and insulin resistance in obese type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We investigated whether GGEx may affect AMP-activated protein kinase ${\alpha}$ ($AMPK{\alpha}$) since $AMPK{\alpha}$ activation is known to stimulate fatty acid oxidation in skeletal muscle of obese rodents. After OLETF rats were treated with GGEx, we studied the effects of GGEx on $AMPK{\alpha}$ and acetyl-CoA carboxylase (ACC) phosphorylation, and the expression of $AMPK{\alpha}$, $PPAR{\alpha}$, and $PPAR{\alpha}$ target genes. The effects of GGEx on mRNA expression of the above genes were also measured in C2C12 skeletal muscle cells. Administration of GGEx to OLETF rats for 8 weeks increased phosphorylation of $AMPK{\alpha}$ and ACC in skeletal muscle. GGEx also elevated skeletal muscle mRNA levels of $AMPK{\alpha}1$ and $AMPK{\alpha}2$ as well as $PPAR{\alpha}$ and its target genes. Consistent with the in vivo data, similar activation of genes was observed in GGEx-treated C2C12 cells. These results suggest that GGEx stimulates skeletal muscle $AMPK{\alpha}$ and $PPAR{\alpha}$ activation, leading to alleviation of obesity and related disorders.

• Endocrinology and Metabolism
• /
• v.37 no.2
• /
• pp.221-232
• /
• 2022

Background Obesity, the prevalence of which is increasing due to the lack of exercise and increased consumption of Westernized diets, induces various complications, including ophthalmic diseases. For example, obesity is involved in the onset of cataracts. Methods To clarify the effects and mechanisms of midodrine, an α1-adrenergic receptor agonist, in cataracts induced by obesity, we conducted various analytic experiments in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a rat model of obesity. Results Midodrine prevented cataract occurrence and improved lens clearance in OLETF rats. In the lenses of OLETF rats treated with midodrine, we observed lower levels of aldose reductase, tumor necrosis factor-α, and sorbitol, but higher levels of hexokinase, 5'-adenosine monophosphate-activated protein kinase-alpha, adenosine 5'-triphosphate, peroxisome proliferator-activated receptor-delta, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, superoxide dismutase, and catalase. Conclusion The ameliorating effects of midodrine on cataracts in the OLETF obesity rat model are exerted via the following three mechanisms: direct inhibition of the biosynthesis of sorbitol, which causes cataracts; reduction of reactive oxygen species and inflammation; and (3) stimulation of normal aerobic glycolysis.

• Korean Journal of Veterinary Research
• /
• v.54 no.1
• /
• pp.21-26
• /
• 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.

• Archives of Plastic Surgery
• /
• v.39 no.2
• /
• pp.106-112
• /
• 2012

Background : Complicated diabetic patients show impaired, delayed wound healing caused by multiple factors. A study on wound healing showed that platelet-rich plasma (PRP) was effective in normal tissue regeneration. Nonetheless, there is no evidence that when platelet-rich plasma is applied to diabetic wounds, it normalizes the diabetic wound healing process. In this study, we have analyzed matrix metalloproteinase (MMP)-2, MMP-9 expression to investigate the effect of PRP on diabetic wounds. Methods : Twenty-four-week-old male Otsuka Long-Evans Tokushima Fatty rats were provided by the Tokushima Research Institute. At 50 weeks, wounds were arranged in two sites on the lateral paraspinal areas. Each wound was treated with PRP gel and physiologic saline gauze. To determine the expression of MMP-2, MMP-9, which was chosen as a marker of wound healing, reverse transcription polymerase chain reaction (RT-PCR) was performed and local distribution and expression of MMP-2, MMP-9 was also observed throughout the immunohistochemical staining. Results : RT-PCR and the immunohistochemical study showed that the levels of MMP-2, MMP-9 mRNA expression in PRP applied tissues were higher than MMP-2, MMP-9 mRNA expression in saline-applied tissues. MMP-9 mRNA expression in wounds of diabetic rats decreased after healing began to occur. But no statistical differences were detected on the basis of body weight or fasting blood glucose levels. Conclusions : This study could indicate the extracellular matrix-regulating effect observed with PRP. Our results of the acceleration of wound healing events by PRP under hyperglycemic conditions might be a useful clue for future clinical treatment for diabetic wounds.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.30 no.3
• /
• pp.521-527
• /
• 2001

The effects of dietary restriction (DR) on antioxidant enzymes were studied in liver, lung and erythrocytes of diabetic rats. Experimental animals used Sprague-Dawley (SD; body weight 350$\pm$20g) male rats and Otsuka Long Evans Tokushima fatty (OLETE; body weight 5--$\pm$30g) male rats, as a model of type 2 diabetes mellitus. Type I diabetes was induced in SD rats by intramuscular injection of alloxan (80 mg/kg BW). Animals were randomly assigned either to continue the ad libitum diet or 40% DR (60% intake of ad libitum diet) groups. The body weight was measured at every 2 weeks to 4 months following DR. The activities of antioxidant enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase (GSHPx) were measured in liver, lung and erythrocytes and the concentration of TBARS as a marker of reactive oxygen species-induced tissue injry was also measured in rats after 4 months 40% DR. The body weight 4 months after 40% DR of control SD, alloxian-diabetid SD and OLETE rats were 80%, 98% and 75% of each control groups, respectively. The activities of SOD, catalase and GSHPx in lung and erythrocytes of rats were not change by 40% DR but in 4 month 40% DR rat liver, the activities of SOD and catalase were increased in control SD, alloxan-diabetic SD, and OLETF groups. The concentration of TBARS in lung and erythrocytes was also not changed by 40% DR, while liver TBARS concentration was decreased in OLETF and control SD rats compared to each non-DR control rats. These results suggested that the body weight changes in diabetic rats by DR was more prominent in type 2 diabetes and changes of antioxidant enzymes is most prominent in liver by DR either type 1 and 2 diabetic rats.

• Korean Journal of Food Science and Technology
• /
• v.46 no.1
• /
• pp.100-107
• /
• 2014

We evaluated preventive effects of Suaeda japonica (SJ) and Spergularia marina Griseb (SMG) on the insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The 10-week old OLETF rats were fed diets containing 3% (w/w) SJ and SMG for 18 weeks. Fasting blood glucose levels in SJ and SMG groups, measured using the oral glucose tolerance test, were lower than that of the control rats. The SMG group showed significantly lower levels of insulin, glycated hemoglobin, triglyceride, and total cholesterol than the control group. In addition, these levels were relatively lower in the SJ group than those in the control rats. The SJ and SMG groups had relatively lower protein levels of nuclear factor-kappa B (NF-${\kappa}B$) p65 in adipose tissue and serine phosphorylated insulin receptor substrate 1 (IRS-1) in skeletal muscle than the control group. These results suggest that SJ and SMG prevent insulin resistance and SMG in particular reduces blood triglyceride and total cholesterol levels.

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