• Korean Journal of Medicinal Crop Science
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• v.16 no.4
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• pp.225-230
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• 2008

Diabetes mellitus is the fifth leading cause of death among Koreans. Control of hyperglycemia and dyslipidemia is strongly correlated with decrease in risks for cardiovascular diseases, the most common and fatal diabetic complication. The effects of chronic feeding of a mixture of Chinese herbs on blood lipid profile were measured in an animal model of type 2 diabetes mellitus, db/db mice (C57BL/Ks). The Chinese herb mixture was composed of Panax ginseng C. A. Meyer,Astragalus membranaceus, Glycyrrhiza uralensis, Lycium chinense, Morus, Pueraria thunbergiana, Prunella vulgaris var. lilacina, Acanthopanax sessiliflorus, Schizandra chinensis, Scutellaria baicalensis, Dioscorea batatas, Polygonatum doratumvar. pluriflorum, Paeonia lactiflora, and Rehmannia glutinosa in a ratio of 1 : 0.7 : 0.4 : 0.7 :0.4 : 0.7 : 1.1 : 0.9 : 0.4 : 0.4 : 0.7 :0.7 : 0.9 : 0.9. Methanol extract of the Chinese herb mixture was tested for the inhibitory activity against yeast ${\alpha}$-glucosidase in vitro. The Chinese herb mixture extract inhibited ${\alpha}$-glucosidase by 25.2% at the concentration of 0.5mg/mL. Four weekold male db/db mice (n = 14) were fed AIN-93G semipurified diet or diet containing 10% powder of the Chinese herb mixture for 6 weeks after 1 week of adaptation period. Body weight (39.5 ${\pm}$ 1.6 g) and food intake (4.3 ${\pm}$ 0.6 g/day) of the Chinese herb group were not significantly different from those of the control group (40.4 ${\pm}$ 2.6 g and 4.5 ${\pm}$ 0.6 g/day). Consumption of Chinese herb mixture significantly decreased plasma glucose level (442.5 ${\pm}$ 36.0mg/dL) compared with the control group (489.8 ${\pm}$ 34.6 mg/dL, p < 0.05). Plasma cholesterol level (159.2 ${\pm}$ 18.4 mg/dL) of the Chinese herb group was significantly lower than that of the control group (185.4 ${\pm}$ 13.7 mg/dL, p < 0.05). Blood glycated hemoglobin (6.3 ${\pm}$ 0.8%) and plasma triglyceride levels (99.4 ${\pm}$ 15.0mg/dL) of the Chinese herb group were not significantly different from those of the control group (6.7 ${\pm}$ 0.7% and 108.8 ${\pm}$ 11.0mg/dL). Thus, the Chinese herb mixture could be useful in the treatment of diabetes and cardiovascular complications of diabetes.

• Journal of Life Science
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• v.22 no.5
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• pp.582-586
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• 2012

The purpose of this study was to examine the effect of 8 weeks of aerobic exercise on serum lipids and kidney function in middle-aged T2DM patients. Subjects participated in aerobic exercise training during 8 wk. They started with an exercise intensity of $HR_{max}$ 60-75%, 20~45 minutes per day, 3~5 times a week. The results were compared to the baseline after 8 weeks. After the 8-week aerobic exercise routine, the body fat percentage and fasting glucose were significantly decreased, and the total cholesterol (TC) andtriglycerides (TG) were significantly decreased. Additionally, kidney function (Blood Urea Nitrogen (BUN], uric acids, and creatinine) was not significantly changed. In conclusion, a regular 8-week aerobic exercise training routine may improve serum lipids; however, kidney function (BUN, uric acids, and creatinine) did not change in middle-age type 2 diabetes mellitus (T2DM) and T2DM in diabetic nephropathy patients.

• IMMUNE NETWORK
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• v.11 no.2
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• pp.107-113
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• 2011

Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.201-207
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• 2011

Peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors and their activation induces regulation of fatty acid storage and glucose metabolism. Therefore, the $PPAR\gamma$ is a major target for the treatment of type 2 diabetes mellitus. In order to generate pharmacophore model, 1080 known agonists database was constructed and a training set was selected. The Hypo7, selected from 10 hypotheses, contains four features: three hydrogen-bond acceptors (HBA) and one general hydrophobic (HY). This pharmacophore model was validated by using 862 test set compounds with a correlation coefficient of 0.903 between actual and estimated activity. Secondly, CatScramble method was used to verify the model. Hence, the validated Hypo7 was utilized for searching new lead compounds over 238,819 and 54,620 chemical structures in NCI and Maybridge database, respectively. Then the leads were selected by screening based on the pharmacophore model, predictive activity, and Lipinski's rules. Candidates were obtained and subsequently the binding affinities to $PPAR\gamma$ were investigated by the molecular docking simulations. Finally the best two compounds were presented and would be useful to treat type 2 diabetes.

• Genomics & Informatics
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• v.21 no.3
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• pp.33.1-33.11
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• 2023

Type 2 diabetes mellitus (T2DM) is a multifactorial, polygenic, and metabolically complicated disease. A large number of genes are responsible for the biogenesis of T2DM and calpain10 (CAPN10) is one of them. The association of numerous CAPN10 genetic polymorphisms in the development of T2DM has been widely studied in different populations and noticed inconclusive results. The present study is an attempt to evaluate the plausible association of CAPN10 polymorphism SNP-19 (rs3842570) with T2DM and T2DM-related anthropometric and metabolic traits in the Noakhali region of Bangladesh. This case-control study included 202 T2DM patients and 75 healthy individuals from different places in Noakhali. A significant association (p < 0.05) of SNP-19 with T2DM in co-dominant 2R/3R vs. 3R/3R (odds ratio [OR], 2.7; p=0.0014) and dominant (2R/3R) + (2R/2R) vs. 3R/3R (OR, 2.47; p=0.0011) genetic models was observed. High-risk allele 2R also showed a significant association with T2DM in the allelic model (OR, 1.67; p=0.0109). The genotypic frequency of SNP-19 variants showed consistency with Hardy-Weinberg equilibrium (p > 0.05). Additionally, SNP-19 genetic variants showed potential associations with the anthropometric and metabolic traits of T2DM patients in terms of body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. Our approach identifies the 2R/3R genotype of SNP-19 as a significant risk factor for biogenesis of T2DM in the Noakhali population. Furthermore, a large-scale study could be instrumental to correlate this finding in overall Bangladeshi population.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.5-20
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• 2008

GLP-1-based drugs (GLP-1 analogues and DPP IV inhibitors) and incretin mimetics are currently one of the most exciting classes of agents for type II diabetes. GLP-1, a gut peptide, is an incretin that potentiates glucose-dependent insulin release from the pancreas, slows GI-transit and stimulates the proliferation of beta-cells. DPP IV inhibitors act like incretins by inhibiting DPP IV which inactivates GLP-1. LC15-0133 is a competitive, reversible DPP IV inhibitor ($IC_{50}$ = 24 nM, Ki=0.247 nM) with excellent selectivity over other critical human proteases such as DPP II, DPP 8, elastase, trypsin. and urokinase. LC15-0133 showed long half-life and good bioavailability in rats and dogs. Inhibition of plasma DPP IV activity by LC15-0133 was kept more than 50% 24 hours after oral dosing in rats and dogs at 0.1 mg/kg and 0.02 mg/kg, respectively. The Minimum effective doses of LC15-0133 were 0.01 mg/kg for lowering blood glucose excursion during oral glucose tolerance test and 0.1 mg/kg for increasing glucose-induced GLP-1 response in C57BL/6 mice. Repeat oral administration of LC15-0133 for 1 month delayed the progression to diabetes and reduced HbA1c levels in a dose-dependent manner in Zucker Diabetic Fatty rats. In conclusion, LC15-0133 is a novel, potent, selective and orally active DPP IV inhibitor and showed an excellent blood glucose lowering effects in various animal models.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.141-150
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• 2014

This study was carried out to investigate the effects of nutrition education on blood glucose in type 2 diabetic patients with low income. There were 50 (27 male and 23 female) study subjects with type 2 diabetes under national medical support, and the monthly income in most of them was less than 500,000 won. Anthropometric measurement, biochemical blood indices, food intake, dietary habits, and nutrition knowledge of the subjects were investigated before nutrition education. Nutrition education was conducted 6 times within 12 weeks. After nutrition education, the glycosylated hemoglobin was significantly decreased (male: $8.4{\pm}1.6%$ to $8.0{\pm}1.7%$, female: $8.3{\pm}1.6%$ to $8.0{\pm}1.3%$) and the total cholesterol was also significantly decreased in both groups. The group of female resulted in a significant decrease in fasting blood glucose ($169.7{\pm}28.2$ mg/dL to $152.8{\pm}22.0$ mg/dL) and triglyceride ($177.8{\pm}56.3$ mg/dL to $162.3{\pm}36.1$ mg/dL), but the group of male did not show a significant decrease in fasting blood glucose and triglyceride. Nutritional knowledge and dietary habit scores of the subjects were significantly improved after nutrition education. The results demonstrate that nutrition education for type 2 diabetic patients with low income are effective in improving their blood glucose.

• Interdisciplinary Bio Central
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• v.4 no.4
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• pp.13.1-13.6
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• 2012

The advanced glycation endproducts receptor (AGER) is a multiligand signal transduction receptor. One of its ligands, S100b molecules activates vascular smooth muscle cells and endothelial cells via its receptor, thus triggering activation of signaling cascades and generation of cytokines and proinflammatory molecules. Ubiquitin-conjugating enzyme Ubc9 is an E2 conjugating enzyme that transfers the activated small ubiquitin-related modifier to protein substrates, and thus it plays a critical role in SUR-Mylation-mediated cellular pathways. Previous studies have shown that both AGE-R and Ubc9 play roles in diverse cellular signaling pathways. However, until recently, little attention has been paid to interactions between AGE-R and Ubc9. In this study, sequence database searches allowed us to identify a potential interaction motif between AGE-R and Ubc9. The subsequent biochemical and molecular biological analysis suggested that there may be specificity in AGE-R and Ubc9 complex signaling in atherosclerosis and cancer cells in a cell-type specific manner. Although the determinant for specificity in AGE-R and Ubc9 complex signaling in cancer cells and atherosclerosis is yet to be determined, this study provides the basis to develop a specific therapeutic application of AGE-R, SURM (small ubiquitin-related modifier)-1, and Ubc9 complex activation pathways in atherosclerosis, diabetes, cancer and inflammatory diseases.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.77-82
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• 2012

AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Its activation requires phosphorylation at Thr-172, which resides in the activation loop of the ${\alpha}1$ and ${\alpha}2$ subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKK${\beta}$ ($Ca^{2+}$/calmodulin-dependent protein kinase kinase${\beta}$). AMPK has been implicated in the regulation of physiological signals, such as in the inhibition of cholesterol fatty acid, and protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on the vascular function and improves vascular abnormalities. AMPK is modulated by numerous hormones and cytokines that regulate the energy balance in the whole body. These hormone and cytokines include leptin, adiponectin, ghrelin, and even thyroid hormones. Moreover, AMPK is activated by several drugs and xenobiotics. Some of these are in being clinically used to treat type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). I reviewed the precise mechanisms of the AMPK activation pathway and AMPK-modulating drugs.

• BMB Reports
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• v.46 no.12
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• pp.567-574
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• 2013

Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed.