• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.327-329
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• 2001

Cordyceps militaris (CM) has been used as a tonics in the traditional medicine. To investigate the anti-diabetic principle of CM, activity guided fractionation was conducted. Hot water extract of CM was fractionated into 3 parts: above 100,000(A), $100,000{\sim}20,000(B)$, below 20,000(C) in molecular weight using in membrane filter system. All fractions showed mild hypoglycemic activity in streptozotocin (STZ)-induced diabetic rats by oral administration (300 mg/kg). The fraction C which was most active among them was fractionated again into two parts, C-1 and C-2 by Sephadex LH 20 column chromatography. The fraction C-1 showed hypoglycemic activity but C-2 did not show activity compared with control in STZ mice. In glucose-fed hyperglycemic mice, fraction C, C-1 and C-2 also showed significant glucose lowering activity. Their decreasing rates of plasma glucose level after 1 hours administrations of fraction C, C-1 and C-2 were 24.5%, 29.3% and 22.0%, respectively (Tolbutamide: 48.4%). These results suggested that CM has both insulin like and insulin release promoting activity and could be developed as an antidiabetic agent.

• YAKHAK HOEJI
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• v.43 no.6
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• pp.818-826
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• 1999

Antidiabetic activity and mechanism of Sangbackpitang (SBPT) was examined in db/db mice, which is a spontaneously hyperglycemic, hyperinsulinemic and obese animal model. SBPT and acarbose were administered orally for 4 weeks. Fasting and non-fasting serum glucose, glycated hemoglobin and triglyceride were all reduced when compared between db/db control group and SBPT treated group. At 12th week after birth, SBPT increased an insulin secretion although statistic significance was not seen. Total activities of sucrase, maltase and lactase in SBPT treated group were all decreased when compared to db/db control. On the other hand, sucrase and maltase activities in acarbose treated groups were increased. Effect of SBPT on mRNA expression of glucose transporter(GLUT-4) was also examined. Quantitation of glucose transporter was performed by RT-PCR and in vitro transcription with co-amplification of rat-action gene as an internal standard. Muscular GLUT-4 mRNA expression in SBPT treated group was increased significantly. These results may suggest that SBPT lowered blood glucose ascribing to inhibition of glycosidase-catalyzed reaction and upregulation of muscular GLUT-4 mRNA expression.

• Journal of the Korean Magnetic Resonance Society
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• v.25 no.3
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• pp.33-38
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• 2021

Type 1 diabetes mellitus (T1DM) is caused by insufficient production of insulin, which is involved in carbohydrate metabolism. Type 2 diabetes mellitus (T2DM) has insulin resistance in which cells do not respond adequately to insulin. The purpose of this study was to estimate the characteristics of type 1 diabetes using streptozotocin-treated mice (STZ-mouse). The sera samples were collected from the models of hyperglycemic mouse and healthy mouse. Based on the pair-wise comparison, five metabolites were found to be noticeable: glucose, malonic acid, 3-hyroxybutyrate, methanol, and tryptophan. It was very natural glucose was upregulated in STZ-mouse. 3-hyroxybutyrate was also increased in the model. However, malonic acid, tryptophan, and methanol was downregulated in STZ-mouse. Several metabolites acetoacetate, acetone, alanine, arginine, asparagine, histidine, lysine, malate, methionine, ornithine, proline, propylene glycol, threonine, tyrosine, and urea tended to be varied in STZ-mouse while the statistical significance was not stratified for the variation. The multivariate model of PCA clearly showed the group separation between healthy control and STZ-mouse. The most significant metabolites that contributed the group separation included glucose, citrate, ascorbate, and lactate. Lactate did not show the statistical significance of change in t-test while it tends to down-regulated both in DNP and Diabetes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1107-1111
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• 2002

This study has been carried out to investigate the effects of the Phenolic compound on the hyperglycemic mice induced with strentozotocin (STZ). The effects of the phenolic compound were assayed by the changes of the blood glucose creatinine and blood urea nitrogen (BUN ) levels, and insulin-immunohistochemical staining and electron microscopical observation for $\beta$ -cells of the Langerhan's islet, under the same experimental conditions. For this purpose male mice were fed with phenolic compound (PA group, IS mg/kg/day; PB group, 90 mg/kg/day)in their diet while the control group received the same commercial diet, for 6 weeks. The blood glucose contents was examined by tail vein blood once a week for 6 weeks. Samples of the pancreas removed after that period were processed for the immunohistochemical identification of $\beta$ -cells as well as for measuring ultrastructural changes of $\beta$-cells. The levels of serum glucose were decreased significantly (p<0.05) on the PB group compared with the control and PA group. The blood BUN and creatinine levels are slightly decreased in the phenolic compound feeding groups compared with control group. The $\beta$-cells on Langerhnan's islet were destructed by administration of STZ, so that a few of insulin-positive cells were observed in the control group. A lot of insulin-positive cells were observed in the PB group compared with the control group. According to the electron microscopical observation $\beta$-cells are recovered from the damage in the PA group. The $\beta$-cell contained a lot of electron dense and pale granules compared with control group. These results suggest that administration of the pear phenolic compound to the mice helped recovery from the damage induced by STZ.

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.2
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• pp.195-201
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• 1995

In this study we wanted to investigate the effect of taurine supplement on the lipid peroxide formation and the activities of glutathione(GSH) dependent enzyme in diabetic model mice. We induce type I diabetes mellitus with alloxan injeciton in ICR mice and type II with high calorie diet in genetically hyperglycemic KK mice. Taurine was given in drinking water at the level of 5%(w/v) for seven days. In type I diabetic model, the malondialdehyde(MDA) of liver and islet significantly increased compared to control group and they significantly decreased by taurine supplement. In type II diabetic model, the concentration of MDA was not changed by taurine supplement. The activities of GSH-peroxidase(GPX) of liver and islet increased in type I diabetic group while decreased in type II. GPX activities were not changed by taurine supplement in the liver of both types but increased in the islet of type II. Taurine supplement has no effect on the activities of GSH S-transferase(GST) in both types. From these results, we suggest that taurine supplement protect against lipid peroxide formation in diabetic model of type I.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.401-408
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• 2011

Type 2 diabetes mellitus (NIDDM) is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. In order to control the type 2 diabetes mellitus, anti-hyperglycemic effect of Triticum aestivum L. water extracts (TAWE) was investigated in 7 week old male diabetic C57BL6/J-ob/ob mice. For the experiments, the diabetic animal model ob/ob mice and non-diabetic animal model lean mice were divided into 3 groups: non-treatment control group (Control), and two experimental groups orally treated with 25 or 100 mg/kg/day dose of TAWE (TAWE-25 and TAWE-100, respectively). The lean mice were used as the non-diabetic normal control. TAWE was orally administrated for 6 weeks and the diabetic clinical markers, including blood glucose level, body weight, organs weight and insulin level were determined. The oral administration of TAWE-100 in ob/ob diabetic mice significantly decreased blood glucose level (78.4%) and body weight (11.9%) compared with diabetic control group. The weights of organs, including spleen, liver, kidneys, heart and lung were not different among groups, while the treatments of TAWE-100 in ob/ob diabetic mice significantly reduced blood total cholesterol (24.35%) and triglyceride (23.97%) levels compared with the diabetic control group. The levels of serum insulin and glucose tolerance were improved after TAWE-100 treatment in ob/ob diabetic mice. Moreover, the immunohistochemical staining for insulin detection in pancreatic islet $\beta$-cells expressed high level of insulin in TAWE-100 treated ob/ob mice. From the above results, the intake of TAWE may be effective in anti-hyperglycemia by the attenuation of glucose and lipid levels. TAWE-containing diets or drugs may be beneficial for controlling diabetes mellitus type 2 in human.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.175-180
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• 2010

Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

• Journal of Yeungnam Medical Science
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• v.36 no.1
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• Nutrition Research and Practice
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• v.17 no.1
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• pp.164-173
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• 2023

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells. MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0-25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. RESULTS: HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. CONCLUSIONS: These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.11
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• pp.1401-1407
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• 2008

1-Deoxynojirimycin (DNJ) is a strong $\alpha$-glucosidase inhibitor which inhibits hyperglycemia in animals. To select the Bacillus strains highly producing DNJ, 4,000 strains were isolated from soil and grain samples. By the inhibitory activity against $\alpha$-glucosidase, nine Bacillus strains were selected and then identified by 16S rDNA sequencing. B. subtilis S10 was finally selected as the best strain for the production of DNJ. Various carbon sources and nitrogen sources in culture medium were evaluated for the highest production of DNJ. As the results, the optimized concentration of carbon source and nitrogen source was 1.0% galactose and 1.6% polypeptone and the concentration of DNJ produced was 0.75 g/L. The effect of culture supernatant of B. subtilis S10 on lowering blood glucose level was investigated in streptozotocin (STZ)-induced diabetic mice model. Mice were randomly assigned to control group (saline) and three test groups such as acarbose group, silkworm powder group and B. subtilis S10 group. After eight-week oral feeding, blood glucose levels of the B. subtilis S10 and silkworm powder groups were respectively $209.1{\pm}19.6\;mg/dL$ (59.1%) and $208.6{\pm}39.8\;mg/dL$ (59.0%) lower than $510{\pm}10\;mg/dL$ of the control group. These results indicated that the culture supernatant of B. subtilis S10 was able to reduce the blood glucose level in STZ-induced diabetic mice.