• Asian-Australasian Journal of Animal Sciences
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• v.31 no.3
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• pp.439-448
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• 2018

Objective: Myogenic satellite cells were isolated from semitendinosus muscle of prepubertal Korean black goat to observe the differential effect of linolenic and retinoic acid in thepresence of thiazolidinediones (TZD) and also to observe the production insulin sensitive preadipocyte. Methods: Cells were characterized for their stemness with cluster of differentiation 34 (CD34), CD13, CD106, CD44, Vimentin surface markers using flow cytometry. Cells characterized themselves as possessing significant (p<0.05) levels of CD13, CD34, CD106, Vimentin revealing their stemness potential. Goat myogenic satellite cells also exhibited CD44, indicating that they possessed a % of stemness factors of adipose lineage apart from their inherent stemness of paxillin factors 3/7. Results: Cells during proliferation stayed absolutely and firmly within the myogenic fate without any external cues and continued to show a significant (p<0.05) fusion index % to express myogenic differentiation, myosin heavy chain, and smooth muscle actin in 2% horse serum. However, confluent myogenic satellite cells were the ones easily turning into adipogenic lineage. Intriguingly, upregulation in adipose specific genetic markers such as peroxisome proliferation-activated receptor ${\gamma}$, adiponectin, lipoprotein lipase, and CCAAT/enhancer binding protein ${\alpha}$ were observed and confirmed in all given treatments. However, the amount of adipogenesis was found to be statistically significant (p<0.01) with linolenic acid as compared to retinoic acid in combination with TZD's. Conclusion: Retinoic acid was found to produce smaller preadipocytes which have been assumed to have insulin sensitization and hence retinoic acid could be used as a potential agent to sensitize tissues to insulin in combination with TZD's to treat diabetic conditions in humans and animals in future.

• BMB Reports
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• v.48 no.9
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• pp.501-506
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• 2015

Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition. [BMB Reports 2015; 48(9): 501-506]

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.629-640
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• 2023

Purpose: Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver which is not a result of excessive alcohol consumption. Its global prevalence was estimated to be approximately 32% in the years 1994-2019. More than half of obese individuals and patients with diabetes are reported to have NAFLD as a comorbidity. This study aimed to investigate the impact of the autumn olive (Elaeagnus umbellata Thunb.) berry on insulin resistance and steatosis in rats fed a high-fructose diet. Methods: Six-week-old Wistar rats were divided into four groups. The control group received a diet consisting of 65% corn starch, while the fructose and experimental groups were fed a diet comprising 65% fructose (FRU) and an FRU diet containing 0.5% (low-dose autumn olive berry group; LAO) or 1.0% (high-dose autumn olive berry group; HAO) ethanol extract of autumn olive berry, respectively, for 10 weeks. Results: The HAO group exhibited significantly lower blood glucose levels compared to the fructose-fed group. Both the LAO and HAO groups showed a substantial reduction in serum insulin levels and insulin resistance when compared to the fructose-fed group. The consumption of LAO and HAO significantly ameliorated dyslipidemia and reduced the levels of triglycerides in the liver compared to the fructose-fed group. Additionally, the consumption of HAO resulted in lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to the fructose group. The hepatic expression of the sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) was significantly reduced in the LAO and HAO groups compared to the fructose group. Conclusion: Autumn olive berries improved steatosis by ameliorating insulin resistance and down-regulating the lipogenesis proteins in rats fed on high fructose diet.

• Journal of Life Science
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• v.25 no.10
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• pp.1081-1090
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• 2015

Diabetes has been one of major health risks in industrialized countries. Allium hookeri is a wild herb distributed in India and Myanmar. The root of the plant has been used as food and medicine in Southeast Asia. We investigated Allium hookeri extract improves type 2 diabetes mellitus in C57BL/KSJ db/db obese mouse. C57BL/KSJ db/db obese mouse arise out of Type 2 diabetes and we treated Allium hookeri methanol extract 400 mg/kg (AH 400), 800 mg/kg (AH 800), positive control group (thiazolidinedine;TZDs) were administered orally for 8weeks. AH treated group normalized lipid enzyme system (triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) and serum glucose, HbA1c and plasma insulin level. AH treated group recovered β-cell damage by hyperglycemia and fatty liver disease. AH treated group significantly up regulated expression of Peroxisome proliferator-activated receptor gamma (PPAR-γ), pyruvate dehydrogenase kinase4 (PDK4), Sterol regulatory element-binding protein 1c (SREBP 1) and fork head box O1 (FOX 01) proteins in C57BL/KSJ db/db obese mouse liver. And we found that AH treated group decreased hepatic malondialdehyde formation in C57BL/KSJ db/db obese mouse liver. These results indicate that Allium hookeri methanol extract might be a potential anti-diabetic agent and could be useful in the treatment of type 2 diabetes mellitus.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.4
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• pp.481-488
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• 2003

Insulin-like Growth Factors (IGFs) and IGF-binding protein act as intra-ovarian regulators that modulate the proliferation and differentiation of the granulosa and theca cells. Moreover, the IGF system is involved in metabolism by modulating the synthesis and degradation of glycogen and protein in animals. However the effect of the IGF system on egg productivity or body growth in KNOC has not been studied in depth. Therefore, this study was performed to investigate differences of serum IGFs and binding protein expressions between two groups showing high and low egg production or body weight and to elucidate the relationship of IGFs with egg productivity and body growth. KNOCs were divided into high and low groups depending on their egg productivity or body growth, and sera were collected every 10 wk from 20 till 60 wk. Serum IGF-I and -II concentration were measured by RIA using human and mouse antiserum and chicken standards. IGFBP was detected by Western ligand blotting. IGF-I concentrations were significantly greater in the high egg production group compared with those in the low egg production group (30 wk, p<0.01; 20 and 40 wk, p<0.05). Also, differences in IGF-II amounts between the two groups were detected at 60 wk (p<0.05). But IGFBPs in the low egg production group were more intense than that in the high egg production group through the egg laying period. The correlation between IGF-I concentration and number of egg production is significantly positive (20 wk, r=0.2729: p<0.05; 40 wk, r=0.3500: p<0.01), while IGF-II shows no correlation with egg productivity. In male KNOC, IGF-I and -II concentrations in the high body weight group are lower than that in the low body weight group. Body weight also shows a negative correlation with the serum IGF-II concentration in male chickens (20 wk, r=-0.5901: p<0.01). Consequently, we suggest that IGFs and binding protein are (in)directly involved in the egg productivity and body growth in KNOC.

• 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.

• Bulletin of the Korean Chemical Society
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• v.31 no.7
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• pp.2019-2024
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• 2010

Insulin-like growth factor binding protein 5 (IGFBP-5) plays an important role in controlling cell survival, differentiation and apoptosis. Apoptosis can be induced by an extrinsic pathway involving the ligand-mediated activation of death receptors such as tumor necrosis factor receptor 1 (TNFR1). To determine whether IGFBP-5 and TNFR1 interact as members of the same apoptosis pathway, recombinant IGFBP-5 and TNFR1 were isolated. The expression and purification of the full-length TNFR1 and truncated IGFBP-5 proteins were successfully performed in E. coli. The binding of both IGFBP-5 and TNFR1 proteins was detected by surface plasmon resonance spectroscopy (BIAcore), fluorescence measurement, electron microscopy, and size-exclusion column (SEC) chromatography. IGFBP-5 indeed binds to TNFR1 with an apparent $K_D$ of 9 nM. After measuring the fluorescence emission spectra of purified IGFBP-5 and TNFR1, it was found that the tight interaction of these proteins is accompanied by significant conformational changes of one or both. These results indicate that IGFBP-5 acts potently as a novel ligand for TNFR1.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.120-128
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• 2005

Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.4
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• pp.471-482
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• 2009

Nutrient availability may control muscle growth directly and indirectly through its influence on regulatory factors. We analyzed the effects of nutrient availability on the breast muscle insulin-like growth factor system. Real time RT-PCR was used to quantify the level of transcription in breast muscle from Langshan (LS) layer and Arbor Acres (AA) broiler chickens subjected to different feeding regimens during embryonic and postnatal development. The AA chickens were fed AA diet (AA, control group) while the LS chickens were either fed LS diet (LL) or AA diet (LA). According to our results, insulin-like growth factor (IGF)-II (embryonic day 16 (E16) - postnatal day 42 (P42)), IGF-I receptor (IGF-IR, E18-P42), and IGF binding protein (IGFBP)-2 (E18-P42), -5 (E16-P14), -7 (E12-P0), and -3 (E12-P0) were positively correlated with IGF-I, while IGFBP-3 (P0-P28) was negatively correlated with IGF-I. In comparison, IGF-IR (E18-P42), IGFBP-2 (E18-P42), IGFBP-5 (E14-P0), and IGFBP-3 (E16-P0) were positively correlated with IGF-II, while IGF-IR (E10-E16) and IGFBP-3 (P0-P28) were negatively correlated with IGF-II. Moreover, IGFBP-2 (E16-P42), -7 (E10-E16), and -3 (E10-E16) were positively correlated with IGF-IR, while IGFBP-3 (P0-P28) was negatively correlated with IGF-IR. Finally, IGFBP-7 (E12-P0) was positively correlated with IGFBP-3, while IGFBP-2 (P0-P28) and -7 (P0-P42) were negatively correlated with IGFBP-3. Overall, the AA chickens exhibited higher levels of IGF-I, IGF-IR, and IGFBP-2 mRNA expression than the LL chickens, while the opposite was true for IGFBP-7. No strain differences in IGF-I, IGF-IR, and IGFBP-7 mRNA expression were detected between LA and AA chickens; however, a strain difference was observed for IGFBP-2. LA chickens exhibited higher levels of IGFBP-2 than LL chickens, while the opposite was true for IGFBP-7. Our data show the first evidence that certain genes may be correlated during specific developmental periods and that strain differences in the expression of those genes in LS and AA chickens are due to differential responses to the same diet.

• BMB Reports
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• v.33 no.6
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• pp.454-462
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• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.