• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.219-225
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• 2022

Glucagon like peptide-1 (GLP-1) released from enteroendocine L-cells in the intestine has incretin effects due to its ability to amplify glucose-dependent insulin secretion. Promotion of an endogenous release of GLP-1 is one of therapeutic targets for type 2 diabetes mellitus. Although the secretion of GLP-1 in response to nutrient or neural stimuli can be triggered by cytosolic Ca²⁺ elevation, the stimulus-secretion pathway is not completely understood yet. Therefore, the aim of this study was to investigate the role of reverse Na⁺/Ca²⁺ exchanger (rNCX) in Ca²⁺ entry induced by muscarinic stimulation in NCI-H716 cells, a human enteroendocrine GLP-1 secreting cell line. Intracellular Ca²⁺ was repetitively oscillated by the perfusion of carbamylcholine (CCh), a muscarinic agonist. The oscillation of cytosolic Ca²⁺ was ceased by substituting extracellular Na⁺ with Li⁺ or NMG⁺. KB-R7943, a specific rNCX blocker, completely diminished CCh-induced cytosolic Ca²⁺ oscillation. Type 1 Na⁺/Ca²⁺ exchanger (NCX₁) proteins were expressed in NCI-H716 cells. These results suggest that rNCX might play a crucial role in Ca²⁺ entry induced by cholinergic stimulation in NCI-H716 cells, a GLP-1 secreting cell line.

• Development and Reproduction
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• v.26 no.4
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• pp.165-174
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• 2022

Three proteins [myosin heavy chain (MHC), filamin-C fragment (FIL-C), and actin 2 (ACT2)] were identified in adductor muscle from diploid and triploid Pacific oysters (Crassostrea gigas) and the relationship between the condition index (CI) and mRNA expression of these genes was investigated, together with the mRNA expression of molluscan insulin-related peptide (MIP), C. gigas insulin receptor-related receptor (CIR), and insulin-like growth factor binding protein complex acid labile subunit (IGFBP-ALS). Monthly changes in the CI were similar to the changes in the tissue weight rate in both groups. ACT2 and MHC mRNA expression was statistically higher in the triploid than the diploid, while FIL-C mRNA expression was significantly higher in the diploid (p<0.05). The MIP, CIR, and IGFBP-ALS mRNA expression of the diploid oysters were all significantly higher in July than in other months (p<0.05). The MIP, CIR, and IGFBP-ALS mRNA expression in the triploid oysters was high in July, but there were no significant differences (p>0.05). Changes in the expression levels of the genes investigated in this study could be used as intrinsic indicators of the annual growth, maturity, and spawning period of cultured diploid and triploid C. gigas in Tongyeong, Korea.

• Clinical Nutrition Research
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• v.13 no.2
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• pp.121-129
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• 2024

The prevalence of metabolic syndrome caused by diets containing excessive fatty acids is increasing worldwide. Patients with metabolic syndrome exhibit abnormal lipid profiles, chronic inflammation, increased levels of saturated fatty acids, impaired insulin sensitivity, excessive fat accumulation, and neuropathological issues such as memory deficits. In particular, palmitic acid (PA) in saturated fatty acids aggravates inflammation, insulin resistance, impaired glucose tolerance, and synaptic failure. Recently, adiponectin, brain-derived neurotrophic factor (BDNF), and glucose-like peptide-1 (GLP-1) have been investigated to find therapeutic solutions for metabolic syndrome, with findings suggesting that they are involved in insulin sensitivity, enhanced lipid profiles, increased neuronal survival, and improved synaptic plasticity. We investigated the effects of adiponectin, BDNF, and GLP-1 on neurite outgrowth, length, and complexity in PA-treated primary cortical neurons using Sholl analysis. Our findings demonstrate the therapeutic potential of adiponectin, BDNF, and GLP-1 in enhancing synaptic plasticity within brains affected by metabolic imbalance. We underscore the need for additional research into the mechanisms by which adiponectin, BDNF, and GLP-1 influence neural complexity in brains with metabolic imbalances.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.8
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• pp.1193-1198
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• 2003

An increase in frequency of administration of exogenous growth hormone (GH) or GH-releasing hormone was reported to be a model to increase blood circulating insulin-like growth factor-1 (IGF-1) and to improve growth performance in animals. We have investigated the effect of twice daily administration of GH-releasing peptide-2 (GHRP-2) on growth performance, GH responsiveness and plasma insulin-like growth factor IGF-1 in swine. We administered to eight swine, 3 control and 5 treatment, a twice daily s.c. injections of GHRP-2 ($30{\mu}g/kg\;BW$) for a period of 10 days. Every day blood samples immediately taken before injections of GHRP-2 or saline, at 08:00 h and 16:00 h, were measured for IGF-1 concentrations. Blood samples for GH assay were collected every 20 min on days 1, 6 and 10, from 1 hour before and 3 h after GHRP-2 or saline injections at 08:00 h. GH peak concentrations and GH area under curve (GH AUC) on day 1, 6 and 10 in treatment group of swine were higher than those in control swine (p<0.05). Twice daily administration of GHRP-2 caused a significantly attenuation (p<0.05) of GH peak concentrations ($80.25{\pm}13.87$, $39.73{\pm}5.72$ and $27.57{\pm}6.06ng/ml$ for day 1, 6 and 10, respectively) and GH AUCs ($3,536.15{\pm}738.35$, $1,310.31{\pm}203.55$ and $934.37{\pm}208.99ng/ml$ for day 1, 6 and 10, respectively). However, there was no significant difference in GH peak concentration and GH AUC between day 6 and 10. Plasma IGF-1 concentration levels were higher in treatment than control group of swine (p<0.05) after 3 days of the treatment, and the levels reached a plateau from day 3 to 10 of experiment. Growth performance did not alter by GHRP-2 administration, even though a numerical increase of body weight gain and feed efficiency was observed. These results indicate that twice daily administration of GHRP-2 for 10 days in swine did not significantly influence on growth performance, caused an overall attenuation of GH response, and that elevation of plasma GH concentrations caused by GHRP-2 administration increased plasma IGF-1 concentrations, even though an attenuation of GH response was observed.

• Journal of the Korean Applied Science and Technology
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• v.35 no.3
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• pp.956-962
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• 2018

Childhood obesity causes a higher risk of obesity, premature death and disability in adulthood. In addition, obese children experience an increased risk of respiratory problems, hypertension, cardiovascular disease, insulin resistance and psychological effects. This study aimed to investigate how an exercise intervention affects health-related physical fitness and inflammatory-related blood factors in obese children after. We hypothesized that there would be positive effects on serum levels of insulin-like growth factor-1 (IGF-1), connecting peptide(C-peptide) and resistin, as well as in muscle and cardiovascular-related physical capacities, after an exercise intervention in obese children. Thirty-seven obese children haveperformed health-related fitness tests and provided blood samples for the analysis of changes in circulating biomarkers, both before and after an 8-week exercise intervention, which includes stretching, aerobic exercise, resistance exercise and sports games. The results indicate that exercise training beneficially affects body compositions, especially percentage body fat and muscle mass, without influencing to body weight and height. The results of the physical fitness tests show that muscle and cardiovascular capacity were increased in obese children in response to exercise training. Simultaneously, the exercise training decreased circulating levels of C-peptide, which equated to a "large" effect size. Although there were no significant effects on the levels of IGF-1 and resistin, they show a "small" effect size. Therefore, our findings suggest that the exercise intervention have beneficial effects on body composition and physical fitness levels in obese children, whichmight be associated with the decline in circulating C-peptide.

• The Korea Journal of Herbology
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• v.29 no.5
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• pp.31-38
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• 2014

Objectives : Egg yolk is composed of various important chemical substances for human health. A calcium shortage causes the growth retardation on the body growth. In this study, we examined the therapeutic effects of calcium, vitamin D and egg yolk peptide (EYP) treatment on the retardation of the longitudinal bone growth induced by low-calcium diet in adolescent rats. Methods : Low calcium diets were administrated for 15 days. During the last five days, calcium and/or vitamin D and/or EYP were administrated. The body weights, longitudinal bone growth rates, the heights of growth plates, and bone morphogenetic protein (BMP)-2 and insulin-like growth factor (IGF)-1 expressions were measured using histochemical analysis. Results : Low calcium diets caused the significant reduction in body weight gains and the longitudinal bone growth. The heights of growth plates and the expressions of BMP-2 and IGF-1 showed the impairment of body growth as well. Calcium and/or vitamin D administration could not significantly increase the longitudinal bone growth. However, calcium, vitamin D, and EYP administration significantly increased the bone growth, the growth plate height, and BMP-2 and IGF-1 expressions. Conclusions : These results suggest that EYP enhances the longitudinal bone growth in the calcium and/or vitamin D deficiency and it could be a promising agent for the treatment of children suffering from malnutrition.

• Journal of Life Science
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• v.13 no.4
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• pp.541-550
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• 2003

E2 glycoprotein of hepatitis C virus (HCV) comprises a surface of viral particle together with E1 glycoprotein, and is thought to be involved in the attachment of HCV viral particle to receptor (s) on the permissible cells including hepatocytes, B cells, T cells, and monocytes. We constructed a phage library expressing cellular proteins of hepatocytes on the phage surface, which turned out to be 8.8${\times}$$10^5$ cfu of diversity and carried inserts in 95% of library. We screened both cDNA phage library and 12-mer peptide library to identify the cellular proteins binding to E2 protein. Some intracellular proteins including tensin and membrane band 4.1 which are involved in signal transduction of survival and cytoskeleton organization, were selected from cDNA phage library through several rounds of panning and screening. On the contrary, membrane proteins such as CCR7, CKR-L2, and insulin-like growth factor-1 receptor were identified through screening of peptide library. Phages expressing peptides corresponding to those membrane proteins were bound to E2 protein specifically as determined by neutralization of binding assay. Since it is well known that HCV can infect T cells as well as hepatocytes, we examined to see if E2 protein can bind to CCR7, a member of C-protein coupled receptor family expressed on T cells, using CCR7 transfected tells. Human CCR7 cDNA was cloned into pcDNA3.1(-) vector and transfected into human embryonic kidney cell, 293T, and expressed on the surface of the cell as shown by flow cytometer. Binding assay of E2 protein using CCR7 transfected cells indicated that E2 protein bound to CCR7 by dose-dependent mode, giving rise to the possibility that CCR7 might be a putative cellular receptor for HCV.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.497-505
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• 2012

To determine the effects of Banggihwanggi-tang(BGHGT) on obesity, the obesity-related factors[gastrin, calcitonin gene related peptide(CGRP), serotonin, ghrelin, obestatin, glucagon-like peptide-1(GLP-1), insulin, orexin, leptin] were investigated in the stomach, pancreas, brain of mice by immunohistochemical(IHC) methods for 4 weeks. The change of body weight was more reduced in BGHGT administered group than that of control group. The IHC density of the gastrin and CGRP positive cells on pylorus was higher in BGHGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach was lower in BGHGT administered group than that of control group. The IHC of GLP-1 positive cells did not observe in the stomach of BGHGT administered groups. The IHC density of GLP-1 in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of insulin positive cells in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of orexin positive neurons in the diencephalon was slightly higher in BGHGT administered group than that of control group. The IHC density of NPY and leptin positive neurons was slightly higher in BGHGT administered group than that of control group. The IHC density of serotonin positive neurons was higher in BGHGT administered group than that of control group. Therefore, we conclude that BGHGT activates appetite inhibitor through appetite related enteroendocrine cells and neuropeptides in stomach, pancreas and brain, and this activation may also be responsible for the inhibition of feeding behavior.

• Clinical and Experimental Reproductive Medicine
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• v.21 no.1
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• pp.83-88
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• 1994

This study was designed to investigate the relationship between insulin resistance and obesity in the pathogenesis of polycystic ovarian syndrome(PCO). Twenty-two women with PCO, of whom thirteen were non-obese with body mass index(BMI, kg/$m^2$) of <25 and nine were obese with BMI${\geq}$25 were studied. Eight non-obese control women and seven obese control women were studied. Serum concentrations of testosterone, lutenizing hormone(LH)/follicle-stimulating hormone(FSH) ratio, and insulin-like growth factor I (IGF-I) were found to be significantly higher(P<0.05) in PCO women compared with control women, which clearly is not related to obesity. Serum glucose, insulin, and C-peptide levels were measured during a 2-hour oral glucose tolerance test(OGTT). Non-obese and obese women with PCO both(P<0.05) compared with control women demonstrated significant hyperinsulinemia after OGTT. The degree of hyperinsulinemia was found to be significantly higher in the obese women with PCO compared with the non-obese women with PCO. We concluded that obesity may contribute to hyperinsulinemia, however may not playa central role in the pathogenesis of PCO.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.201-209
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• 2018

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.