• Nutrition Research and Practice
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• v.9 no.1
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• pp.22-29
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• 2015

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2-fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic ${\beta}$-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic ${\beta}$-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.348-356
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• 2011

Liriope platyphylla is a medical herb that has long been used in Korea and China to treat cough, sputum, neurodigenerative disorders, obesity and diabetes. The aims of this study were to study the antidiabetic effects of the aqueous extract of L. platyphylla (AEtLP) through pancreatic and extrapancreatic actions. AEtLP were orally administrated to ICR mice once a day for 7 days. Of three different concentrations of AEtLP, only 10% AEtLP were low toxic to liver, based on body weight and serum biochemical analyses. However, 10% AEtLP-treated mice displayed signifi cant reduction of the glucose concentration and increased insulin concentration; no changes were noted using 5% and 15% AEtLP. Also, the increase of glucose transporter (Glut)-1 expression in liver was dependent on the concentration of AEtLP, and was regulated by the phosphorylation of Akt. The lowest expression of Glut-3 was observed in 15% AEtLP treated mice, followed by 10% AEtLP- and 5% AEtLP-treated mice. This pattern of Glut-3 expression was roughly in accord with the phosphorylation of c-Jun N-teminal kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway. Furthermore, a signifi cant rise of the superoxide dismutase activity (SOD) was detected in AEtLP-treated mice. The fi ndings suggest that AEtLP should be considered as a diabetes therapeutic candidate to induce insulin secretion from pancreatic ${\beta}$-cells and glucose uptake in liver cells.

• KSBB Journal
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• v.21 no.6 s.101
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• pp.466-473
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• 2006

Impaired insulin secretion from pancreatic beta-cells in response to glucose is an important feature in the pathology of non-insulin-dependent diabetes mellitus (NIDDM). In the course of screening for useful insulin secretagogues, we have isolated and identified YHB-2017 (Genistein) as a insulin secretion potentiator from fermentation broths of our in-house microbial library. The insulinotropic activity of YHB-2017 in isolated rat pancreatic islets was exerted only at high concentration of glucose (8.3-16 mM) but not at low concentration of glucose (3.3-5.5 mM). Also, in perifusion study with isolated rat pancreatic islets, YHB-2017 stimulated insulin secretion in a time-dependent manner when YHB-2017 was added to KRB buffer containing 16 mM glucose. In the presence of $200\;{\mu}M$ diazoxide and 35 mM KCI, which stimulates maximum $Ca^{2+}$ influx independently of KATP channel, YHB-2017 enhanced KATP channel-independent insulin secretion at high concentration glucose (16 mM). To elucidate the mechanisms of the glucose-dependent potentiation effect of YHB-2017, pharmacologic inhibitors for protein kinase A, protein kinase C and calcium/calmodulin kinase II were pre-treated and then the potentiation effect of YHB-2017 on insulin secretion was investigated. Pre-treatment of H89 as a PKA inhibitor had a significant inhibitory effect on YHB-2017-induced potentiation effect. Furthermore, western immunoblotting analyses revealed that YHB-2017 increased phosphorylation of PKA substrates and cAMP response element-binding protein (CREB) under high concentration of glucose. These results demonstrated that the insulinotropic effect of YHB-2017 is mediated through PKA signal pathway and activated amplifying $K_{ATP}$ channel-independent insulin secretion pathway.

• Nutrition Research and Practice
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• v.15 no.3
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• pp.294-308
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• 2021

BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.477-483
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• 2023

The flowers of Carthamus tinctorius (Safflower) were extracted with 80% aqueous methanol (CTex) and the concentrates were partitioned into EtOAc (CTE), n-BuOH (CTB), and H₂O (CTW) fractions. Repeated silica gel (SiO₂) and octadecyl silica gel column chromatographies for the EtOAc and n-BuOH fractions led to isolation of four flavonol glycosides. Nuclear magnetic resornance, infrarad spectroscopy, and mass spectroscopy revealed the chemical structure of the isolated compounds, astragalin (1), isoquercetin (2), nicotiflorin (3), and rutin (4). Quantitative analysis of four isolated compounds in CTex was performed by HPLC. CTex was found to contain 1 at 0.107, 2 at 0.367, 3 at 6.752, and 4 at 0.991 mg/g, respectively. Through this study, an experiment was conducted to evaluate the protective effect on pancreatic islets of the extract, solvent fractions, and all isolated compounds using a zebrafish larvae damaged by alloxan. Pancreatic islet size treated with EtOAc (CTE), n-BuOH (CTB), and H₂O (CTW) fractions and compounds 1-4 significantly increased compared to the alloxan-induced group. These results indicate that C. tinctorius flowers and its isolated compounds are used as potential anti-diabetic agents.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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• pp.367-386
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• 2012

Objectives : The object of this study was to observe the effects of Gamioryung-san (GOS), which consists of 22 types of herbs, on streptozotocin (STZ)-induced diabetic nephropathy rats. Methods : Three different dosages of GOS were orally administered once a day for 28 days from 3 weeks after STZ treatment. Six groups, each of 8 rats per group were used. Changes on the body weights, blood glucose levels, serum BUN and creatinine levels, urine volumes, and UAER were observed with changes on the kidney malondialdehyde contents and glutathione, dismutase and catalase contents. In addition, histopathology of kidney, pancreas, thymus and spleen were observed. The results were compared with antioxidant silymarin 100 mg/kg, of which the effects on STZ -induced diabetes and related complications are already confirmed. Results : As a result of treatment of GOS 800, 400 or 200 mg/kg for 28 days, STZ-induced decreases of body weights, hyperglycemia, atrophic changes of pancreatic islets with decreases of insulin-immunoreactive cells and decreases of glucagon -immunoreactive cells were inhibited dose-dependently. Increases in kidney weight, serum BUN and creatinine levels, urine volumes, UAER, vasodilated atrophic glomerulus and abnormal tubules were inhibited dose-dependently. Also increases of kidney MDA contents and decreases of GSH contents, SOD and CAT activities, decreases of thymus and spleen weights, and atrophic changes at histopathological observation were also inhibited. The effects of GOS 400 mg/kg showed similar effects to silymarin 100 mg/kg. Conclusions : These results suggest that 400 mg/kg of GOS retarded the STZ-induced diabetic nephropathies as similarly to silymarin 100 mg/kg, through modulations of oxidative stress and immune systems.

• Nutritional Sciences
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• v.6 no.4
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• pp.209-215
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• 2003

This research was performed to investigate the effects of the supplementation of multi-extracts of mori folium (MF) and of exercise on blood lipid profiles and tissue differentiation in streptozotocin (STZ)-induced diabetic rats. The animal groups consisted of a normal-control group, a STZ-control group, three STZ-induced diabetic groups supplemented ad libitum with various amounts of MF extracts (MF-720, MF-360, and MF-180 groups), and a STZ-induced diabetic group supplemented with MF-360 combined with exercise; eight male Sprague-Dawley rats, 4 weeks old, were assigned to each experimental group and were raised in the laboratory for a 10 week experimental period. The MF supplementation group showed a significant reduction in levels of serum total cholesterol and triglyceride compared to the STZ-control group. HDL-cholesterol levels were significantly increased in the MF supplementation group compared to STZ-control group. The ratio of HDL-cholesterol to total cholesterol was significantly higher in MF supplementation group compared to the STZ-control group. The Atherogenic Index (AI) values in the MF supplementation groups were found to be significantly lower than in the STZ-control group. Serum AST and ALT levels were significantly reduced in the MF-supplementation groups compared to the STZ-control group. Total cholesterol level in the liver tissue was significantly decreased in the MF-360 group and in the MF-360 + exercise group compared to the STZ-control group. In immunohistochemical staining of the pancreatic islets of the MF-supplemented groups, a significantly higher number of insulin-immunoreactive cells were observed compared to the STZ-control group. In the MF supplementation groups, Bowman's capsules were clearly observed as hypertrophy of the glomeruli was not obvious. In the MF supplementation groups, a relative reduction in the hypertrophy of the basement membrane of the glomeruli and a significant reduction in the mesangium were observed compared to the STZ-control group. The results of this study suggest that supplementation of MF has beneficial effect in improving plasma lipid and tissue metabolism in streptozotocin-induced rats.

• Herbal Formula Science
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• v.21 no.2
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• pp.110-120
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• 2013

Objectives : The object of this study was to observe the pharmacological effects of Yookmijihwang-tang-gamibang (Liuweidihuang-tang-jiaweifang, YGB) consisted of 17 types of herbs has been traditionally used in Korean medicine for treating various disorders in clinics, aqueous extracts on the genetically obese and type II diabetic C57BL/6JHam-ob/ob(ob/ob) mice. Methods :Three different dosages of YGB were orally administered, once a day for 28 days to ob/ob mice with ob/ob control and C57BL/6JJms normoglycemic intact mice. Four weeks after treatments of YGB: the changes on the body weight, food consumption, blood glucose levels, leptin and adiponectin contents were observed for monitoring the antiobese and antidiabetic effects of YGB. The effects were compared to those of CLA(conjugated linoleic acid) which improve type II diabetes and inhibit related obesity. Results : After end of 28 days of continuous treatments, ob/ob control showed increases of adipocyte hypertrophy, vasodilated atrophic glomerulus which were detected with marked hyperplasia of pancreatic islets, insulin and glucagon producing cells. These obese and related type II diabetes induced in ob/ob mice were markedly and significantly inhibited by 28 days of continuous treatment of three dosages of YGB. The YGB 50mg/kg showed similar favorable effects on the diabetes and related diabetic complications as compared with CLA 750mg/kg in ob/ob mice of the present study. Conclusions : The results obtained in this study suggest that over 25mg/kg of YGB extracts favorably retarded the obese and type II diabetes in genetically obese and type II diabetic ob/ob mice.

• Nutrition Research and Practice
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• v.7 no.2
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• pp.103-108
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• 2013

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ${\beta}$-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.

• Journal of the Korean Applied Science and Technology
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• v.1 no.1
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• pp.37-47
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• 1984

Effects of garlic on hypocholesterolemia, anticoagulation and hypoglycemia were studied in the present experiments using male rats. The results were summarized as follows. 1. The supplementation of $2{\sim}4%$ garlic to 2% cholesterol diets did not affect food intake and weight gain in male rats. 2. Rat's groups fed the diets supplemented with $2{\sim}3%$ garlic (C.D.E.F) to 2% cholesterol diet (B) decreased serum total cholesterol levels by $16{\sim}32%$, triglyceride levels by $18.6{\sim}26.8%$ and ${\beta}/{\alpha}-lipoportein$ rations by $42{\sim}58%$, but increased HDL-cholesterol levels by $29{\sim}65%$ as compared to B group, and so the author assumes that garlic supplementation exerts hypocholesterolemic effect on cholesterol - fed rats because of the increase of HDL and HDL - cholesterol levels. 3. Rat's groups fed the diets supplemented with $2{\sim}4%$ garlic (C.D.E.F) to 2% cholesterol plus 0.25% bile salt diet (B) increased whole blood coagulation times, prothrombin times and fibrinolytic activities, but decreased plasma fibrinogen levels as compared to B group, and so the author assumes that garlic supplementation exerts anticoagulative effect because of the inhibition of fibrinogen synthesis in male rat's liver. 4. Rat's groups fed the diets supplemented with $2{\sim}4%$ garlic (B.C.D.E) to standard diet (A) decreased serum glucose levels by $1{\sim}24%$, but increased serum insulin concentrations by $0.5{\sim}3.0$ times as compared to A group, and so the author assumes that garlic supplementation exerts hypoglycemic effect because of the increase of serum insulin levels by stimulation pancreatic secretion of insulin from ${\beta}-cells$ in the islets of Langerhans.