• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.762-768
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• 2020

This study aimed to investigate the effect of ladder-climbing exercise training on neurobiological markers in the hippocampus of mice with type 2 diabetes (T2DM). Twenty-one C57BL/6 male mice were randomly assigned to the non-diabetic control (NDC, n = 7), diabetic control (DC, n = 7), and diabetic training (DT, n = 7) groups. The DT group performed ladder-climbing training (LCT) five times a week for eight weeks. We measured the levels of hippocampal neurobiological markers (catalase [CAT], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], amyloid-beta [Aβ], tau, and CC motif chemokine ligand 11 [CCL11]). The BDNF levels were significantly higher in the DT group than in the DC group (p < 0.05). The Aβ and CCL11 levels were significantly higher in the DC group than in the NDC and DT groups (p < 0.05). The tau levels were significantly higher in the DC group than in the NDC group (p < 0.05). However, there was no significant difference in CAT and NGF levels among the groups (p > 0.05). These results suggest that while T2DM could induce neurodegeneration, LCT may be effective in alleviating neurodegeneration caused by T2DM.

• Journal of Korean Biological Nursing Science
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• v.24 no.2
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• pp.77-85
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• 2022

Purpose: Aging process comes with cognitive impairment due to decreased neuronal cell number, activity, and neuronal circuit. Alteration of inhibitory neurons contributes to cognitive impairment in normal aging and is responsible for disrupting the excitation/inhibition balance by reducing the synthesis of gamma-aminobutyric acid (GABA). Morus nigra (Mulberry) is a natural physiologically active substance that has been proven to have anti-oxidant, anti-diabetic, and anti-inflammatory effects through many studies. This study aimed to evaluate the effects of the mulberry extract (ME) on cognitive function through anti-oxidant enzyme and GABAergic neuronal activity in aged rat brain. Methods: Sprague Dawley rats were randomly assigned as the young group (8 weeks, n= 8), aging group (67 weeks, n= 8), and aging+ mulberry extract group (67 weeks, n= 8). The aging+ mulberry extract group was orally administered 500 mg/kg/d mulberry extract for 6 weeks. Results: The aging+ mulberry extract group improved spatial and short-term memory. The antioxidant potential of ME increased the expression of superoxide dismutase-1 (SOD-1) and decreased inducible nitric oxide synthase (iNOS). Also, the aging+ mulberry extract group significantly increased the expression of GABAergic interneuron in hippocampus cornu ammonis1 (CA1) compared to the aging group. Conclusion: The number of GABAergic inhibitory interneurons was deceased and memory functions in the aging process, but those symptoms were improved and restored by mulberry extract administration.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.493-497
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• 2013

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to $30{\mu}g$ of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

• Clinical Nutrition Research
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• v.6 no.3
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• pp.172-182
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• 2017

We investigated the association between dietary habits/food group consumption patterns and early risk of metabolic syndrome (MetS), a main cause for metabolic disease. Study participants were recruited from the health promotion center in Dong-A University Hospital and public advertisement. Study subjects (n = 243, 21-80 years) were categorized into three groups: Super-healthy (MetS risk factor [MetS RF] = 0, n = 111), MetS-risk carriers (MetS RF = 1-2, n = 96), and MetS (MetS $RF{\geq}3$, n = 27). Higher regularity in dietary habits (breakfast-everyday, regular eating time, non-frequent overeating, and non-frequent eating-out) was observed in the Super-healthy group than in the MetS-risk carriers, and particularly in the MetS subjects. The relationship between food group consumption patterns and MetS-risk related parameters were investigated with adjustment for confounding factors. Fruit consumption was positively associated with HDL-cholesterol, and tended to be negatively associated with waist circumference, triglyceride, LDL-cholesterol, and insulin resistance (IR). The consumption of low-fat meats and fish, and vegetables was negatively associated with hs-CRP. Specifically, the consumption of seafoods belonging to the low-fat fish was negatively associated with fasting glucose, hs-CRP, and interleukin (IL)-6. Anchovy/dried white baits consumption was negatively associated with fasting insulin and IR. Green-yellow vegetables consumption was negatively associated with fasting insulin, IR, and hs-CRP. On the other hand, sugars and fast-foods were positively associated with LDL-cholesterol. Additionally, fast-foods consumption was positively associated with hs-CRP and IL-6 levels. In conclusion, dietary habits/food group consumption patterns are closely associated with MetS-risk related parameters in Koreans. It may suggest useful information to educate people to properly select healthy foods for early prevention of MetS.

• BMB Reports
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• v.53 no.2
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• pp.100-105
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• 2020

While liver histopathology is heterogeneous in diabetes, the underlying mechanisms remain unclear. We investigated whether glycemic variation resulting from differential diets can induce heterogeneity in diabetic liver and the underlying molecular mechanisms. We generated end-stage non-obese diabetic model rats by subtotal-pancreatectomy in male Sprague-Dawley rats and ad libitum diet for 7 weeks (n = 33). The rats were then divided into three groups, and fed a standard- or a low-protein diet (18 or 6 kcal%, respectively), for another 7 weeks: to maintain hyperglycemia, 11 rats were fed ad libitum (18AL group); to achieve euglycemia, 11 were calorie-restricted (18R group), and 11 were both calorie- and protein-restricted with the low-protein diet (6R group). Overnight-fasted liver samples were collected after the differential diets together with sham-control (18S group), and histology and molecular changes were compared. Hyperglycemic-18AL showed glycogenic hepatopathy (GH) without steatosis, with the highest GSK-3β inactivation because of Akt activation during hyperglycemia; mitochondrial function was not impaired, compared to the 18S group. Euglycemic-18R showed neither GH nor steatosis, with intermediate GSK-3β activation and mitochondrial dysfunction. However, euglycemic-6R showed both GH and steatosis despite the highest GSK-3β activity and no molecular evidence of increased lipogenesis or decreased ApoB expression, where mitochondrial dysfunction was highest among the groups. In conclusion, heterogeneous liver histopathology developed in end-stage non-obese diabetic rats as the glycemic levels varied with differential diets, in which protein content in the diets as well as glycemic levels differentially influenced GSK-3β activity and mitochondrial function in insulin-deficient state.

• Korean Journal of Veterinary Research
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• v.50 no.2
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• pp.105-111
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• 2010

Carnosine is a dipeptide $(\beta-alanyl-L-histidine)$ found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels, glucose tolerance test (GTT), glycosylated hemoglobin, and serum biochemical and lipid levels in streptozotocin-induced diabetic mice. There were five experimental groups including normal (ICR mice), control (saline), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w.. Carnosine was orally administered to the diabetic mice everyday for 12 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine at the dose of 6 mg/kg significantly decreased the blood glucose level compared with the control at 2 and 4 weeks. The treatments of carnosine at the doses of 6 and 30 mg/kg significantly decreased the blood glucose levels in GTT and glycosylated hemoglobin compared with the control. Carnosine significantly increased total proteins compared with the control. Carnosine at the dose of 6 mg/kg significantly decreased total cholesterol and triglyceride in the serum compared to the control. These results suggest that carnosine at a low level has a hypoglycermic effect resulting from reduction of blood glucose and that a carnosine-containing diet or drug may give a benefit for controlling diabetes mellitus in humans.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.309-318
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• 2015

Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

• Journal of Life Science
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• v.20 no.7
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• pp.1012-1018
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• 2010

The aim of this study was to determine whether Alzheimer's amyloid precursor protein (APP) is dysregulated in adipose tissues of C57BL/6 male mice by high-fat diet (HFD) induced obesity, aging, or streptozotocin (STZ)-induced diabetes. APP mRNA expression was examined by quantitative real-time PCR (QPCR) in subcutaneous (SAT) and epididymal adipose tissues (EAT) from mice in 8 different condition groups. By combining conditions of age (16 weeks/26 weeks of age), diet (normal diet (ND)/high-fat diet), and induction of diabetes (non-diabetic/diabetic), 88 mice were divided into 8 different groups. QPCR demonstrated that APP expression in SAT was significantly increased by about two-fold in HFD-induced obese mice compared to both 16 week-old and 26 week-old mice in the ND group (16 weeks p=0.001; 26 weeks p<0.0001), but no changes in EAT was found. Particular effects of aging on APP gene expression were not observed in either adipose tissue depots. Significantly decreased APP expression was found in SAT in STZ-induced diabetic mice fed on ND or HFD at 16 weeks of age (ND p<0.05; HFD p<0.01). Linear regression analysis demonstrated that APP expression levels correlated with body weight in both the non-diabetic group (R=0.657, p<0.0001, n=39) and the diabetic group (R=0.508, p=<0.0001, n=49), but did not correlate with plasma glucose levels, which suggests that decreased APP expression in STZ-induced diabetic mice is most likely due to weight loss rather than hyperglycemia. These data confirm APP dysregulation by weight changes in humans and suggest a possible role linking midlife obesity with the later development of amyloidogenesis in the brain of older patients with Alzheimer's disease.

• Toxicological Research
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• v.29 no.1
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• pp.7-14
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• 2013

Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.8
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• pp.1182-1187
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• 2005

This study was designed to investigate the supplementary effects of Lentinus edodes which were harvested at different time period and part on acetylcholine content and its related enzyme activities in the brain of diabetic mouse model (KK mouse). We fed mice with standard diet (Control diet; CON) or 4 different kinds of experimental diets (DGC: on time harvested, cap of Dong Go; DGS: on time harvested, stipe of Dong Go; HSC: late harvested, cap of Hyang Sin: HSS: late harvested, stipe of Hyang Sin) to KK mouse for 8 weeks. Neurotransmitter such as acetylcholine contents, acetylcholinesterase activities, monoamine oxidase-B ac-tivities and lipid peroxide contents in the brain were measured. The results showed that acetylcholine content was significantly higher in DGC and HSC groups than CON group. The activities of acetylcholinesterase and monoamine oxidase-B enzyme were significantly inhibited in the brain of DGC and HSC groups compared with CON group. Lipid peroxide content was lower in DGC group than CON group. These results suggested that the cap of Lentinus edodes which were harvested on time and late time contain increased acetylcholine content and decreased acetylcholinesterase activities, monoamine oxidase-B activities and lipid peroxide contents. Thus the cap of Lentinus edodes which were harvested at different time periods may play an effective role in enhancing cognitive function.