G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.
Objectives: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats. Methods: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks. Diabetic rats were divided into ECA-150, ECA-300 and Metformin (MET)-180 groups, where the numbers are the doses in mg.kg.bw administered to the groups. Normal (NC) and diabetic (DC) controls were given distilled water. The animals had their fasting blood glucose levels and body weights determined every 7 days for 21 days. Oral glucose tolerance tests (OGTTs) were carried out in all animals at the beginning and the end of the experiment. Liver and kidney samples were harvested for glucose 6 phosphatase (G6Pase) and hexokinase activity analyses. Small intestines and diaphragms from normal rats were used for ${\alpha}-glucosidase$ and glucose uptake studies against the extract. Results: Two doses, 150 and 300 mg/kg bw, significantly reduced the fasting blood glucose levels in diabetic rats and helped them maintain normal body weights. The glucose level in DC rats significantly increased while their body weights decreased. The 150 mg/kg bw dose significantly increased hexokinase and decreased G6Pase activities in the liver and the kidneys. ECA inhibited ${\alpha}-glucosidase$ activity and promoted glucose uptake in the rats' hemi-diaphragms. Conclusion: This study revealed that ECA normalized blood glucose levels and body weights in type 2 diabetic rats. The normalization of the glucose levels may possibly be due to inhibition of ${\alpha}-glucosidase$, decreased G6Pase activity, increased hexokinase activity and improved glucose uptake by muscle tissues.
Guava ($Psidium$$guajava$) contain a great deal of polyphenol compound and work on the treatment of $Diabetes$$mellitus$ effectively. In this study, the bioactivities of aqueous extract (GLEx) of guava leaf were investigated. Total phenolic contents of GLEx was 266.9 mg tan/g. The effects of GLEx on digestive enzymes, ${\alpha}$-amylase, maltase and sucrase were investigated. $IC_{50}$ values of GLEx against ${\alpha}$-amylase, maltase and sucrase were 0.65 mg/$m{\ell}$, 2.0 mg/$m{\ell}$ and 3.5 mg/$m{\ell}$ respectively. The effect of GLEx on oral glucose tolerance test (OGTT) was performed in normal ICR mouse, control (dstilled water) and GLEx (aqueous extract of Guava leaf) were co-administered orally with glucose, showed reducing effect on the blood glucose level. The guava is likely to useful for prevention or improvement of hyperglycemia by lowering the blood glucose level and inhibiting glycoside hydrolase activity.
This study was performed to determine the effect of Takju(Korean turbid rice wine) lees on the serum glucose level in streptozotocin-induced diabetic rats. 24 Sprague-Dawley male rats were divided into three groups: normal control(NC), diabetic control(DC) and diabetic rats(DS) were fed on experimental diet and water ad libitum for 4 weeks. DS diet was containing 20% Takju lees. Body weight gain and food Efficiency Ratio(FER) were significantly lower in DC and DS than NC. DS tended to have higher weight, weight gain and FEF than DC nevertheless food intake. Therefore Takju lees could possibly complement casein as a protein source. Gastrointestianl transit time in DS significantly decreased than NC while not significantly than DC. Serum lipid profiles and AST. ALT and amylase were not significantly different between diabetic DC and DS. Blood glucose was measured at fasting state and 30, 60, 90 and 120 minute by oral glucose tolerance test, DS tended to lower the mean(${\pm}$ SE) incremental blood glucose concentrations than DC and was significantly low at 120 min. But incremental AUG(area under the curve) of postprandial glucose response was not significantly different. In conclusion, in spite of high contents of carbohydrate Takju lees perhaps have a benefit effect on the diabetes.
Yan Sun;Hai Qu;Xiaohong Niu;Ting Li;Lijuan Wang;Hairui Peng
The Korean Journal of Physiology and Pharmacology
/
v.28
no.1
/
pp.1-10
/
2024
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.
Osteoarthritis (OA) of the temporomandibular joint (TMJ) is a severe form of temporomandibular disorders (TMDs), presenting gradual breakdown of articular cartilage and subchondral bone by the functional load sustained to exceed the physiologic tolerance of the joint. In such a joint loaded, offensive bioactive materials such as matrix degrading proteins, cytokines, and free radicals increase in concentration to shift the tissue response in the joint to degeneration from regeneration or remodeling. Recently, it has been issued that obesity can play an offensive role in pathogenesis of OA in a metabolic way. Adipokines released by adipose cells are present at higher concentration in the arthritic joint and joints of obese individuals. However, because of conflicting data reported, further scientific study should be performed to elucidate the practical role of adipokines in pathogenesis of TMJ OA. As far as the clinical signs and symptoms of TMJ OA are not much different from those of other forms of TMD and any definitive treatment modality to control directly the bone resorptive activity is not available yet, the treatment of TMJ OA should be directed to reduce the physical load and enhance the physiologic tolerance of the joint by means of conservative treatment such as physical therapy, medication, and occlusal splint therapy for sufficient period and, if needed after that, supplementary surgical procedure such as intra-articular injection, arthrocenthesis, and arthroscopic surgery that have turned out to be effective to control OA signs and symtpoms. Enthusiastic reassurance and motivation for patients to control behaviors for themselves to reduce unnecessary functional load in daily life is very important for the joint to reach to more favorable orthopedic stability of the TMJ more quickly, guaranteeing more successful management TMJ OA.
Kim, Jin Sook;Lee, Jung Mi;Kim, Seung Joon;Lee, Sook Young;Kwon, Soon Seog;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Song, Jeong Sup;Park, Sung Hak
Tuberculosis and Respiratory Diseases
/
v.57
no.5
/
pp.425-433
/
2004
Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.
Journal of Korean Academy of Oral and Maxillofacial Radiology
/
v.27
no.2
/
pp.91-103
/
1997
The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human epidermoid carcinoma A-253 cell line using semiautomated MTT assay. 2,4,6,8,10 Gy were irradiated at a dose rate of 210 cGy/min using /sup 60/Co Irradiator ALDORADO 8. After irradiation, A-253 cell lines(2×10⁴cells/mil were exposed to bleomycin or cisplatin for 1 hour. The viable cells were determined for each radiation dose with/without 2 /lg/mi of drug at the 3rd day. And they were compared to control values. The results were obtained as follows : 1. The surviving curve with gentle slope was obtained after irradiation of 2, 4, 6, 8, 10 Gy on A-253 cell line. 2. The cytotoxicity of bleomycin or cisplatin at the concentration of 2㎍/ml was great on A-253 cell line. But, there was no significant difference between the cytotoxicity of bleomycin and that of cisplatin. 3. There were significant differences of surviving fractions after irradiation with 2㎍/mi of bleomycin compared with irradiation only on A-253 cell line. 4. There were significant differences of surviving fractions after irradiation with 2㎍/ml of cisplatin compared with irradiation only on A-253 cell line. 5. There were no significant differences of surviving fractions between the groups of irradiation with bleomycin and the groups of irradiation with cisplatin on A-253 cell line.
Purpose: Food Allergen Immunotherapy (Oral) is a form of immunotherapy administered to patients who are allergic to foods such as egg, milk, and peanut. The food allergen is orally administered to the patient in an escalating dose for desensitization or tolerance development. The safety and effectiveness of the therapy were assessed using a systematic literature review and meta-analysis. Methods: For a literature search, 8 national databases and a number of international databases including Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library were used; and 13 articles (all from international databases) were selected. The target of Food Allergen Immunotherapy (Oral) included patients with food allergy, and the intervention was food allergen immunotherapy without limiting the food type. The safety and effectiveness of Food Allergen Immunotherapy (Oral) were assessed by reviewing all the articles reporting on the therapy. The control group received standard therapies including aversion therapy, no treatment, anti-histamine treatment, and placebo. Safety was assessed through the incidence of complication and emergency medication. Effectiveness was assessed based on therapy success rate, symptomatic improvement, and quality of life. Results: Although Food Allergen Immunotherapy (Oral) was shown to have successful desensitization in patients with food allergy, the safety of the technique has not yet reached an acceptable level; the possible reason is due to the high rate of complication and frequency of emergency medication. Also, each study employed varying protocols while relying on a small number of participants and a short monitoring period. Conclusion: The results of assessment suggest that the level of evidence from current literature review is low and further research is necessitated for the verification of the safety and effectiveness of the therapy (Grade of Recommendation: A; Level of Technology: II-b).
Journal of Korean Academy of Oral and Maxillofacial Radiology
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v.28
no.1
/
pp.271-283
/
1998
The purpose of this study was to aid in the prediction of tumor cell tolerance to radiotherapy and/or chemotherapy. For this study, cell surviving curves were obtained for human squamous cell carcinoma KB cell line after radiation exposure and/or administration of antitumor drugs. 2, 4, 6, 8, 10Gy were irradiated at a dose rate of 210cGy/min using /sup 60/Co Irradiator ALDORADO 8. After irradiation, KB cell lines (3×104cells/ml) were exposed to 2㎍/ml of bleomycin or cisplatin for 1 hour. The viable cells were determined by MTT assay for each radiation dose and/or each drug at the 4th day. And they were compared to control values. The obtained results were as follows : 1. The slope of the surviving curve after irradiation of 2, 4, 6, 8, 10Gy on KB cell line was relatively steep. 2. There was no significant difference between the cytotoxicity of bleomycin compared to control group. But, there was significant difference between the cytotoxicity of cisplatin compared to control group. And the cytotoxicity of cisplatin was greater than that of bleomycin on KB cell line. 3. There were significant differences of surviving fractions after irradiation of 2Gy and 10Gy with 2㎍/ml of bleomycin compared with the groups of irradiation only on KB cell line. 4. There were significant differences of surviving fractions after irradiation of 2, 4, 6, 8, 10Gy with 2㎍/ml of cisplatin compared with the groups of irradiation only on KB cell line. 5. There was significant difference of surviving fraction between groups after irradiation of 10Gy with 2㎍/ml of bleomycin and cisplatin.
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