• Asian-Australasian Journal of Animal Sciences
• /
• 제29권5호
• /
• pp.731-738
• /
• 2016

Glucagon-like peptide-2 (GLP-2) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this research was to determine the protective effect of GLP-2 mediated TJ and transepithelial electrical resistance (TER) in lipopolysaccharide (LPS) stressed IPEC-J2 cells and to test the hypothesis that GLP-2 regulate TJ and TER through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway in IPEC-J2 cells. Wortmannin and LY294002 are specific inhibitors of PI3K. The results showed that $100{\mu}g/mL$ LPS stress decreased TER and TJ proteins occludin, claudin-1 and zonula occludens protein 1 (ZO-1) mRNA, proteins expressions (p<0.01) respectively. GLP-2 (100 nmol/L) promote TER and TJ proteins occludin, claudin-1, and zo-1 mRNA, proteins expressions in LPS stressed and normal IPEC-J2 cells (p<0.01) respectively. In normal cells, both wortmannin and LY294002, PI3K inhibitors, prevented the mRNA and protein expressions of Akt and mTOR increase induced by GLP-2 (p<0.01) following with the significant decreasing of occludin, claudin-1, ZO-1 mRNA and proteins expressions and TER (p<0.01). In conclusion, these results indicated that GLP-2 can promote TJ's expression and TER in LPS stressed and normal IPEC-J2 cells and GLP-2 could regulate TJ and TER through the PI3K/Akt/mTOR pathway.

• 비만대사연구학술지
• /
• 제1권1호
• /
• pp.4-13
• /
• 2022

Currently, pharmacotherapy is becoming essential for obesity, owing to its expanding and increasing epidemiology. In this review, novel peptide-based drugs of four classes are covered: GLP-1 receptor agonist, GIP/GLP-1 receptor dual agonist, glucagon/GLP-1 receptor dual agonist, and a combination of amylin receptor agonist/GLP-1 receptor agonist. Semaglutide is a next-generation GLP-1 receptor agonist with a longer duration and stronger weight and glucose reduction effects than liraglutide and dulaglutide. In the STEP1 trial, semaglutide 2.4 mg reduced body weight by approximately 15% in people with obesity with similar or milder adverse events than liraglutide 3.0 mg. Tirzepatide, a GIP/GLP-1 receptor dual agonist, also has a long duration and strong weight- and glucose-lowering effect. According to SURPASS-2, 3, and 4, in patients with BMI≥25 kg/m² and type 2 diabetes mellitus (T2DM), tirzepatide 15 mg reduced the initial body weight by >13%. Cotadutide, a glucagon/GLP-1 receptor dual agonist, showed weaker weight-lowering effects than semaglutide and tirzepatide, while it was comparable to that of liraglutide in a phase 2 clinical trial for non-alcoholic fatty liver disease in patients with BMI≥25 kg/m² and T2DM. Additionally, its effect on the liver was noticeable. The long-acting amylin receptor agonist cargrilintide combined with semaglutide can be another effective option for obesity treatment. Even in a small phase 1 trial with a short study period of 20 weeks, cargrilintide 2.4 mg/semaglutide 2.4 mg reduced by 17% of initial body weight in people with BMI 27-39.9 kg/m². In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.

• 한국축산식품학회지
• /
• 제33권1호
• /
• pp.1-8
• /
• 2013

The effects of adding goldenrod leaf powder (GLP) and goldenrod stem powder (GSP) (0.1% and 0.5%) to raw ground pork on antioxidant activity were examined. The following six treatment groups were used: Control (without antioxidant), GLP1 (with 0.1% GLP), GLP2 (with 0.5% GLP), GSP1 (with 0.1% GSP), GSP2 (with 0.5% GSP) and AS (with 0.05% ascorbic acid). The chemical compositions, pH values, instrumental color, conjugated diene (CD), free fatty acids (FFA) and thiobarbituric acid-reactive substance (TBARS) value were measured during 15 d of storage at chilled temperatures. The addition of GLP and GSP showed no effect on moisture, protein and fat contents of the samples. However, adding 0.5% GSP increased the ash contents of ground pork (p<0.05). The pH values of treated samples decreased until day 7, and then increased thereafter. The addition of GLP and GSP decreased the $L^*$ and $a^*$ values and increased the $b^*$ value (p<0.05). The CD, FFA and TBARS value of the control were higher (p<0.05) than samples containing GLP and GSP. The addition of GLP and GSP resulted in a significant decrease in CD, FFA and TBARS values. Overall, this study demonstrated that GL and GS could be used as an antioxidant of raw ground pork.

• Asian-Australasian Journal of Animal Sciences
• /
• 제27권5호
• /
• pp.733-742
• /
• 2014

The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ) proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets' intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK) signaling pathway in piglets' intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco's modified Eagle's medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs' jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.

• 한국임상약학회지
• /
• 제21권2호
• /
• pp.57-65
• /
• 2011

Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide delay gastric emptying, increasing satiety, and enhance insulin secretion. Two new classes of treatments related to incretin hormones for the management of type 2 diabetes mellitus have emerged: GLP-1 receptor agonists (e.g., exenatide, liraglutide) and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin, alogliptin), which prevent the degradation of GLP-1. A MEDLINE search was conducted in order to evaluate the efficacy and safety of incretin-based therapies and publications were reviewed. Data from clinical trials indicated incretin-based treatment showed clinically significant reductions in hemoglobin A1c with low risk of hypoglycemia. Weight reductions were observed with GLP-1 receptor agonists where as DPP-4 inhibitors are weight neutral.

• 한국버섯학회지
• /
• 제7권3호
• /
• pp.105-109
• /
• 2009

최근 국제원자재가 상승에 따라 버섯 배지 가격이 50% 이상 상승하여 톱밥 대체 배지의 개발이 절실한 실정으로 충남도내에서 생산되는 은행잎부산물을 이용하여 버섯 배지로 개발하여 생산비 절감 및 경제적 이익 창출을 도모하기 위해 수행한 결과를 요약하면 다음과 같다. 은행잎박을 10~30% 첨가량에 따른 균사생장은 대조구 102 mm/28일에 비해 은행잎박 10~30% 첨가시 86~101mm/28일로 균사생장이 느린 경향이었으며, 균배양일수는 은행잎박 10~20% 첨가시 29일로 대조구와 같았다. 초발이 소요일수는 은행잎박 10~20% 첨가시 7일, 생육 일수는 11일로 대조구와 같았지만, 은행잎박 30% 첨가시 초발이소요일수는 1일정도 늦었다. 갓의 크기는 은행잎박 첨가시 대조구에 비해 작은 경향이 있었고, 대의 길이는 은행잎박 10% 첨가시 98mm로 대조구 91mm에 비해 길었다. 대의 두께는 대조구 45mm에 비해 은행잎박 10~30% 첨가시 45~48mm로 두꺼운 경향이었다. 대의 경도는 대조구 32,156($g/cm^2$)에 비해 은행잎박 10~30% 첨가시 $35,062g/cm^2{\sim}41,065g/cm^2$로 높아 저장 및 유통에 유리하였고, 병당 수량은 대조구 85.8g/병에 비해 은행잎박 10~30% 첨가시 88.7~95.6g/병으로 3~11% 증수되었다. 따라서 큰느타리 병재배시 은행잎박 10%를 첨가하는 것이 수량 증수 효과가 있는 것으로 사료된다.

• Toxicological Research
• /
• 제27권3호
• /
• pp.133-135
• /
• 2011

The FDA guidance focuses on the use of the NOAEL to establish the maximum recommended starting dose. The majority of NOAEL has been described inaccurately or incompletely in final reports for 90-days repeated dose toxicity test based on GLP (good laboratory practice) regulation. This is the most serious one of reasons for why most pharmaceutical companies targeting global markets have disregarded the final report produced from GLP facilities in Korea. The problems in deciding NOAEL reflected in the final reports are mainly due to the followings; 1) Inaccurate description or use of NOEL, NOAEL and LOAEL, 2) Insufficient and inappropriate interpretations in findings from toxicity test. This paper is intended to provide the insight into distinguishing NOAEL from NOEL and LOAEL, and into classifying findings from toxicity test. Here, the three step method is newly suggested by applying the weight-based classification to the NOEL, NOAEL and LOAEL based on the findings.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권9호
• /
• pp.3981-3986
• /
• 2014

Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels ($[Ca^{2+}]i$) were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular $Ca^{2+}$ elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.

• Bulletin of the Korean Chemical Society
• /
• 제31권12호
• /
• pp.3760-3764
• /
• 2010

We screened 10,000 heterocyclic small molecules and identified a novel hit core skeleton of 3-(8-chloro-6-(trifluoromethyl) imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives. It has been selected as a potential glucagon-like peptide 1 receptor (GLP-1R) activator and demonstrated its effects in increasing GLP-1 secretion, and thereby increasing the glucose responsiveness in both in vitro and pharmacology analyses. Further studies are currently underway to optimize the potency and selectivity of 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives (hit compounds 2 and 8), and address their in vivo efficacy and therapeutic potential. These molecules may serve as useful evidence showing that compounds with a 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate moiety are selective GLP-1R agonists, and have potential as anti-diabetic treatment agents.

• Journal of Gastric Cancer
• /
• 제20권3호
• /
• pp.256-266
• /
• 2020

Purpose: This study aimed to examine the early postprandial changes in gastrointestinal (GI) hormones and hemodynamics in terms of early dumping syndrome after gastrectomy for gastric cancer. Materials and Methods: Forty patients who underwent gastrectomy for gastric cancer and 18 controls without previous abdominal surgery were enrolled. Before and 20 minutes after liquid meal ingestion, blood glucose, glucagon-like peptide-1 (GLP-1), and GLP-2 concentrations and superior mesenteric artery (SMA) and renal blood flow were measured. The patients' heart rates were recorded at 5-minute intervals. All subjects were examined for dumping syndrome using a questionnaire based on Sigstad's clinical diagnostic index. Results: The postprandial increases in blood glucose, GLP-1, and GLP-2 levels as well as SMA blood flow and heart rate were greater in patients who underwent gastrectomy than in controls (all P<0.010). Patients who underwent gastrectomy showed a significantly decreased renal blood flow (P<0.001). Among patients who underwent gastrectomy, distal gastrectomy was a significant clinical factor associated with a lower risk of early dumping syndrome than total gastrectomy (hazard ratio, 0.092; 95% confidence interval, 0.013-0.649; P=0.017). Patients who underwent total gastrectomy showed a greater postprandial increase in blood glucose (P<0.001), GLP-1 (P=0.030), and GLP-2 (P=0.002) levels as well as and heart rate (P=0.013) compared to those who underwent distal gastrectomy. Conclusions: Early postprandial changes in GI hormones and hemodynamics were greater in patients who underwent gastrectomy than in controls, especially after total gastrectomy, suggesting that these changes play a crucial role in the pathophysiology of early dumping syndrome.