• BMB Reports
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• v.49 no.3
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• pp.139-148
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• 2016

In the past decade, the incidence of type 2 diabetes (T2D) has rapidly increased, along with the associated cardiovascular complications. Therefore, understanding the pathophysiology underlying T2D, the associated complications and the impact of therapeutics on the T2D development has critical importance for current and future therapeutics. The prevailing feature of T2D is hyperglycemia due to excessive hepatic glucose production, insulin resistance, and insufficient secretion of insulin by the pancreas. These contribute to increased fatty acid influx into the liver and muscle causing accumulation of lipid metabolites. These lipid metabolites cause dyslipidemia and non-alcoholic fatty liver disease, which ultimately contributes to the increased cardiovascular risk in T2D. Therefore, understanding the mechanisms of hepatic insulin resistance and the specific role of liver lipids is critical in selecting and designing the most effective therapeutics for T2D and the associated co-morbidities, including dyslipidemia and cardiovascular disease. Herein, we review the effects and molecular mechanisms of conventional anti-hyperglycemic and lipid-lowering drugs on glucose and lipid metabolism.

• Korean Journal of Animal Reproduction
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• v.26 no.4
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• pp.321-328
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• 2002

The hormone resistin is associated with type II diabetes mellitus in rodent model. Resistin impairs glucose tolerance and insulin action. A new class of anti-diabetic drugs were called thiazolidinediones (TZDs) downreguates a resistin. Resistin gene expression is induced during adipocyte differentiation and resistin polypeptide is secreted by adipocytes. But, the correlation between increased adiposity and resistin remains unknown. The objectives of this study was to clone a mouse resistin CDNA and to generate transgenic mice overexpressing mouse resistin gene. The pCMV-mus/resistin gene was prepared from previous recombinant pTargeT$^{TM}$-mus/resistin by digestion of Bgl II, and has used for microin- jection into pronuclei of one cell embryos. Mouse resistin expression was detected in transgenic F$_1$mice by RT-PCR. The transgenic mouse with resistin gene expression has heavier body weight which was measured higher level of plasma glucose than that of normal mouse. And in diet-induced experiments, in fasting group, resistin expression was higher than that of re-feeding group. This result demonstrates that the resistin gene overexpressing mice may be became to obesity and be useful as an animal disease model to be diabetes caused by insulin resistance of resistin.n.

• Journal of The Korean Ophthalmological Society
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• v.60 no.2
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• pp.144-151
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• 2019

Purpose: Intravitreal aflibercept, ranibizumab, bevacizumab, and dexamethasone are the most widely used drugs in the treatment of diabetic macular edema (DME). The aim of this study was to compare the efficacy and safety of anti-vascular endothelial growth factors and dexamethasone for the treatment of DME. Methods: There were nine previous systematic reviews on this topic; we updated these high-quality reviews. Seven studies were added to two studies following a literature search. Efficacy outcomes were 1) average improvement in visual acuity, 2) proportion of patients who experienced an improvement in vision (an increase in best-corrected visual acuity (BCVA) of ${\geq}15$ in the Early Treatment Diabetic Retinopathy Study [ETDRS]), and 3) proportion of patients who experienced worsening vision (a decrease in BCVA of ${\geq}15$ in the ETDRS). Safety outcomes included systemic adverse events and ocular-related adverse events. Results: The mean difference in the BCVA for ranibizumab versus bevacizumab treatment was 0.16 (95% confidence interval [CI]: -0.02, 0.34), and that for ranibizumab versus aflibercept was -0.08 (95% CI: -0.26, 0.10). The mean difference in the change of BCVA for aflibercept versus ranibizumab was -0.20 (95% CI: -0.40, -0.01), and that for aflibercept versus bevacizumab was -0.34 (95% CI: -0.53, -0.14). Other efficacy outcomes showed similar trends, and there was no significant difference between treatments. There was also no significant difference in both systemic and ocular adverse events rates between the treatments. Conclusions: In DME patients, the efficacy of aflibercept was found to be higher with respect to BCVA changes compared with ranibizumab or bevacizumab. However, there were no significant difference in terms of visual acuity improvement or visual acuity of more than 15 letters, nor in terms of anti-vascular endothelial growth factors (as a safety outcome).

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.12
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• pp.1858-1864
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• 2014

In the present investigation, the anti-diabetic potential of 80% ethanol extract of Eleutherococcus senticosus leaves (EEES) was examined based on ${\alpha}$-glucosidase inhibitory activities. EEES was sequentially fractionated with n-hexane, chloroform, ethyl acetate (EtAOc), n-butanol, and $H_2O$. Of the various fractions, EtAOc fraction effectively inhibited ${\alpha}$-glucosidase activity by 68.05%. Therefore, EtAOc fraction was selected for further isolation and identification studies. EtAOc fraction was separated by medium pressure liquid chromatography with silica and ODS gel to yield eight fractions (EAA~EAH). Based on the results of ${\alpha}$-glucosidase inhibitory activity, EAH fraction was re-chromatographed to yielded four more fractions (EAHA~EAHD). Of these, EAHC fraction showed higher ${\alpha}$-glucosidase inhibitory activity of 93.60%. EAHC fraction was re-chromatographed and yielded EAHCA and EAHCB fractions. Further, identification and chemical structures of these two fractions were analyzed using $^1H$-NMR, $^{13}C$-NMR, and mass spectra data. Based on the results of the spectral data, the isolated compounds were identified as hyperoside and isoquercetin. Results of the present study indicate that the isolated compounds, hyperoside, and isoquercetin from leaves of E. senticosus could be used for the development of new anti-diabetic drugs.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.391-397
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• 2009

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 in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), 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 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

• Journal of Veterinary Clinics
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• v.27 no.4
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• pp.348-365
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• 2010

Artemisia capillaries THUNB is a perennial herb that belongs to the family compositae spp. and the most common plant among the various herbal folk remedies used in treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. The object of this study is to observe the dosage-dependent anti-obestic effects of an aqueous extracts of dried aqueous extracts of stems of Artemisia capillaris Thunberg. [Artemisiae capillaris Herba, In-Jin in Korean, INJ] on 45%/Kcal high fat diet (HFD) supplied mice. 45%/Kcal rodent HFD are supplied to ICR mice from 1 week before initiation of INJ administration throughout the 12 weeks, and after the end of 12 weeks of 62.5, 125 and 250 mg/kg/day of INJ administration, the efficacy was divided into five categories 1) hypoglycemic, 2) hepato-protective, 3) nephroprotective, 4) hypolipemic, and 5) anti- obesity effects. The effects were compared to those of simvastatin (for hypolipemic activity), silymarin (for hepatoprotective and free radical scavenger effects) and metformin (for hypoglycemic and related anti-obesity effects). 7 animals per group (8 groups; total 56adapted mice on HFD were selected base on the body weight at 6 days after initiation of HFD supply) were used in this experiment. INJ and all three different reference drugs were directly suspended or dissolved in distilled water, and administered at a volume of 10 mL/kg, once a day for 84 days from 1 week after HFD supply. As results of 91 days of continuous HFD supply, mice showed marked obese states, hyperglycemia, hyperlipemia, liver damages and kidney damages. These mean the obesity, diabetes, diabetic hepatopathies, nephropathies and hyperlipemia were induced by HFD supply. After end of 84 days of continuous treatment of three different dosages of INJ, all diabetes related complications were inhibited; relatively favorable anti-obesity, hypolipemic, hepatoprotective, hypoglycemic and nephroprotective effects. These favorable effects showed relatively good dose-relations between all three different dosages of INJ treated, and INJ 250 mg/kg showed enough favorable effects on diabetes and related four complications tested as compared with one of each three different references. Otherwise, the efficacy of 62.5 and 125 mg/kg of INJ was somewhat slighter than those of all three reference drugs. Therefore, the suitable effective dosage of INJ is considered as 250 mg/kg/day in the present study. The overall anti-obesity effects of INJ 250 mg/kg-treated group was similar or more favorable than those of metformin 250 mg/kg-treated group, and INJ 250 mg/kg showed slighter hypoglycemic effects with silymarin 100 mg/kg and metformin 250 mg/kg, similar hypolipemic effects with simvastatin 10 mg/kg, and similar hepatoprotective effects with silymarin 100 mg/kg, and similar nephroprotective effects with that of silymarin 100 mg/kg and metformin 250 mg/kg, respectively. Obese, hyperglycemia, hyperlipemia, steatohepatitis and related nephropathies induced by HFD supply were dramatically inhibited by 84 days of continuous treatment of all three different dosages of INJ. It is, therefore expected that INJ extracts will be a favorable alternative agent for diet-related diabetes and complications.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.99-99
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• 2002

The hormone resistin is associated with typeII diabetes mellitus in rodent model. Resistin impairs glucose tolerance and insulin action. A new class of anti-diabetic drugs were called thiazolidinediones (TZDs) downregulates a resistin which is induced during adipocyte differentiation. But the connection between increased adiposity and resistin remains unknown. The objectives of this study was to clone a mouse resistin cDNA and to generate transgenic mice overexpressing mouse resistin gene. The 555 bp of mouse resistin was amplified from mob cDNAS by polymerase chain reaction (PCR) and cloned into pCR$\^$(R)/ 2.1 TOPO T-vector. Mouse resistin mRNA on the basis of Genbank sequence (acession no. AF323080). Then, the PCR product was cloned into pTargeT$\^$TM/ mammalian expression vector that has pCMV promoter and chimeric intron. Restriction enzyme analysis with BamH I and Not I was carried out to determine an orientation of the insert in the vector. The pCMV-mus/resistin gene was prepared from previous recombinant pTargeT$\^$TM/-mus/resistin by digestion of Bgl II, and has used for microinjection into pronuclei of one cell embryos. The microinjected embryos were transfered to pseudopregnant foster-mother. Mouse resistin expression was detected in transgenic F1 mice by Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR). Resistin gene expression mouse has heavier body weight which was measured higher level of plasma glucose than that of normal mouse. And in diet-induced experiments, the abdominal fat pads were isolated from each 24h starvation and re-feeding after fasting group mice that were assessed by RT-PCR analysis. In fasting group mice, resistin expression was higher than that of re-feeding group mice. This result suggests that the resistin gene overexpressing mice may be became to obesity and be useful as an animal disease model to be diabetes mellitus caused by insulin resistance of resistin.

• Analytical Science and Technology
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• v.32 no.2
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• pp.35-47
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• 2019

In this study, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed to detect 26 antidiabetic compounds in adulterated dietary supplements using a simple, selective method. The work presented herein may help prevent incidents related to food adulteration and restrict the illegal food market. The best separation was obtained on a Shiseido Capcell Pak(R) C18 MG-II ($2.0mm{\times}100mm$, $3{\mu}m$), which improved the peak shape and MS detection sensitivity of the target compounds. A gradient elution system composed of 0.1 % (v/v) formic acid in distilled water and methanol at a flow rate of 0.3 mL/min for 18 min was utilized. A triple quadrupole mass spectrometer with an electrospray ionization source operated in the positive or negative mode was employed as the detector. The developed method was validated as follows: specificity was confirmed in the multiple reaction monitoring mode using the precursor and product ion pairs. For solid samples, LOD ranged from 0.16 to 20.00 ng/mL and LOQ ranged from 0.50 to 60.00 ng/mL, and for liquid samples, LOD ranged from 0.16 to 20.00 ng/mL and LOQ ranged from 0.50 to 60.00 ng/mL. Satisfactory linearity was obtained from calibration curves, with $R^2$ > 0.99. Both intra and inter-day precision were less than 13.19 %. Accuracies ranged from 80.69 to 118.81 % (intra/inter-day), with a stability of less than 14.88 %. Mean recovery was found to be 80.6-119.0 % and less than 13.4 % RSD. Using the validated method, glibenclamide and pioglitazone were simultaneously determined in one capsule at concentrations of 1.52 and 0.53 mg (per capsule), respectively.

• Food Science and Industry
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• v.51 no.4
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• pp.278-301
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• 2018

Although more than 80% of living organisms are found in marine ecosystems, only less than 10% of marine resources have been utilized for human food consumptions and other usages. It is well known that marine resources (fish, shellfish and algae) have exceptional nutritional properties; however, their functional characteristic has not been completely discovered. It is believed that metabolites (organic compounds, proteins, peptides, lipids, minerals, etc.) play an important role to show its biological properties. Marine proteins and peptides are considered to be future drugs due to their excellent biological activities with a fewer adverse side effect. Marine peptides show several biological activities, including antimicrobial, antioxidant, anti-inflammatory, anti-cancer, anti-viral, anti-tumor, anti-diabetic, anti-hypertensive, anti-coagulant, immunomodulatory, appetite suppressing and neuroprotective effects. Therefore, the pharmaceutical, nutraceutical, and cosmeceutical companies have been paid attention to the marine peptides to commercialize into products. This current review mainly focused on the above mentioned biological activities of marine peptides and protein hydrolysates as a functional food and pharmaceutical applications. To commercialize these materials in industrial level required large quantity in high-purity level, and it is complicated to produce huge quantity from the marine resources due to insufficient raw materials, unavailability of raw materials through a year, hinder the growth with geographical variations, and availability of compounds in extreme small quantities. The best solution for these issues is to introduce new modern technologies such as artificial intelligence robots, drones, submersibles and automated raw material harvesting vessels in farming industries instead of man power, which will lead to 4th industrial revolution.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.2
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• pp.153-160
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• 2016

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.