• Asian-Australasian Journal of Animal Sciences
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• v.30 no.8
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• pp.1190-1197
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• 2017

Objective: Adipose tissue is no longer considered as an inert storage organ for lipid, but instead is thought to play an active role in regulating insulin effects via secretion adipokines. However, conflicting reports have emerged regarding the effects of adipokines. In this study, we investigated the role of adipokines in glucose metabolism and insulin sensitivity in obese Bama mini-pigs. Methods: An obesity model was established in Bama mini-pigs, by feeding with high-fat and high-sucrose diet for 30 weeks. Plasma glucose and blood biochemistry levels were measured, and intravenous glucose tolerance test was performed. Adipokines, including adiponectin, interleukin-6 (IL-6), resistin and tumor necrosis factor alpha ($TNF-{\alpha}$), and glucose-induced insulin secretion were also examined by radioimmunoassay. AMP-activated protein kinase (AMPK) phosphorylation in skeletal muscle, which is a useful insulin resistance marker, was examined by immunoblotting. Additionally, associations of AMPK phosphorylation with plasma adipokines and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed by Pearce's correlation analysis. Results: Obese pigs showed hyperglycemia, high triglycerides, and insulin resistance. Adiponectin levels were significantly decreased (p<0.05) and IL-6 amounts dramatically increased (p<0.05) in obese pigs both in serum and adipose tissue, corroborating data from obese mice and humans. However, circulating resistin and $TNF-{\alpha}$ showed no difference, while the values of $TNF-{\alpha}$ in adipose tissue were significantly higher in obese pigs, also in agreement with data from obese humans but not rodent models. Moreover, strong associations of skeletal muscle AMPK phosphorylation with plasma adiponectin and HOMA-IR index were obtained. Conclusion: AMPK impairment induced by adiponectin decrease mediates insulin resistance in high-fat and high-sucrose diet induction. In addition, Bama mini-pig has the possibility of a conformable model for human metabolic diseases.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.113-120
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of micovascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate thε effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$ and AUC. Administration of glipizide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, $k_{a},\;t_{1/2},\;t_{max}$ and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in $t_{1/2}\;and\;t_{max}$, and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.5
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• pp.463-471
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• 2005

Recently, the number of diabetic patients have been increased with westernized living way and meal habitation. The regulation of blood sugar concentration is very important for diabetic patients to keep homeostasis and, to prevent acute or chronic complications. Epinephrine combined with lidocaine is used in dental clinic extensively. And epinephrine combined with lidocaine also effects on decreasing the blood leakage volume by constricting micro vessle and arteriole. But, So far there are few researches about the effect of epinephrine contained in dental local anesthetic agent on the blood sugar of diabetes during minor oral surgery. The purpose of this study was intended to investigate whether epinephrine which combined with dental local anesthetics influence body glucose level in diabetes patients by glucose monitoring. The subject of this study were 38 diabetic patients and 38 normal adults, each patient was checked body glucose after a meal 2 hours later with resting state, and injection 1:100000 epinephrine with dental lidocaine 54 ml or lidocaine 54 ml only. And then the body glucose level was checked 5 minutes and 30 minutes after injection. The results were analyzed by two way ANOVA test (p<0.05). The results were as follows: In the experimental group 1, the mean of the blood sugar level was 180.3 mg/dl before an anesthetic injection, 182.8 mg/dl after 5minutes of the anesthetic injection and 182.2 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05). In the experimental group 2, the mean of the blood sugar level was 237 mg/dl before an anesthetic injection, 234.5 mg/dl after 5minutes of the anesthetic injection and 231.8 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05). In the controlled group 1, the mean of the blood sugar level was 117.6 mg/dl before an anesthetic injection, 119.1 mg/dl after 5minutes of the anesthetic injection and 129.3 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05). In the controlled group 2, the mean of the blood sugar level was 104.2 mg/dl before an anesthetic injection, 102 mg/dl after 5minutes of the anesthetic injection and 105.3 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05).

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.395-402
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• 2009

Insulin appears to play a role in brain physiology, and disturbances of cerebral insulin signalling and glucose homeostasis are implicated in brain pathology. The objective of the present study was to investigate the protective effects of insulin under conditions of oxidative stress induced by hydrogen peroxide ($H_2O_2$) in C6 glial cells. Insulin at concentration of $10^{-7}$ M could prevent 12 h $H_2O_2$-induced cell death. The formation of reactive oxygen species (ROS), nitric oxide (NO) and 2-thiobarbituric acid-reactive substances (TBARS) were significantly scavenged by insulin pre-treatment in C6 glial cells after $H_2O_2$-induced oxidative stress. Insulin significantly stimulated the phosphorylation of Akt in the cells and the activation of Akt was maintained in response to insulin under $H_2O_2$ incubation for 12 h. In conclusion, these results provide evidence that insulin acts as a free radical scavenger and stimulating Akt activity. These data suggest that insulin may be effective in degenerative diseases with oxidative stress.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.589-594
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• 2016

Insulin is a peptide hormone of the endocrine pancreas and exerts a wide variety of physiological actions in insulin sensitive tissues, such as regulation of glucose homeostasis, cell growth, differentiation, learning and memory. However, the role of insulin in osteoblast cells remains to be fully characterized. In this study, we demonstrated that the insulin (100 nM) has the ability to stimulate the phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK) and the levels of inhibin-${\beta}E$ in the osteoblast-like UMR-106 cells. This insulin-stimulated activities were abolished by the PI3K and MEK1 inhibitors LY294002 and PD98059, respectively. This is the first report proving that insulin is a potential candidate that enables the actions of inhibin-${\beta}E$ subunit of the TGF-${\beta}$ family. The current investigation provides a foundation for the realization of insulin as a potential stimulator in survival signaling pathways in osteoblast-like UMR-106 cells.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.4-9
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• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4867-4871
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• 2012

Cervical cancer is a leading cause of morbidity and mortality in women worldwide. Although the human papillomavirus (HPV) is considered the major causative agent of cervical cancer, yet the viral infection alone is not sufficient for cancer progression. The etiopathogenesis of cervical cancer is indeed complex; a precise understanding of the complex cellular/molecular mechanisms underlying the initiation, progression and/or prevention of the uterine cervix is therefore essential. Autophagy is emerging as an important biological mechanism in targeting human cancers, including cervical cancer. Furthermore, autophagy, a process of cytoplasm and cellular organelle degradation in lysosomes, has been implicated in homeostasis. Autophagic flux may vary depending on the cell/tissue type, thereby altering cell fate under stress conditions leading to cell survival and/or cell death. Autophagy may in turn govern tumor metastasis and subsequent carcinogenesis. Inflammation is a known hallmark of cancer. Vascular insufficiency in tumors, including cervical tissue, leads to depletion of glucose and/or oxygen perturbing the osmotic mileu causing extracellular acidosis in the tumor microenvironment that may eventually result in autophagy. Thus, targeted manipulation of complex autophagic signaling may prove to be an innovative strategy in identification of clinically relevant biomarkers in cervical cancer in the near future.

• BMB Reports
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• v.47 no.7
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• pp.393-398
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• 2014

The role of Bax inhibitor-1 (BI-1) in the protective mechanism against apoptotic stimuli has been studied; however, as little is known about its role in death receptor-mediated cell death, this study was designed to investigate the effect of BI-1 on Fas-induced cell death, and the underlying mechanisms. HT1080 adenocarcinoma cells were cultured in high concentration of glucose media and transfected with vector alone (Neo cells) or BI-1-vector (BI-1 cells), and treated with Fas. In cell viability, apoptosis, and caspase-3 analyses, the BI-1 cells showed enhanced sensitivity to Fas. Fas significantly decreased cytosolic pH in BI-1 cells, compared with Neo cells, and this decrease correlated with BI-1 oligomerization, mitochondrial $Ca^{2+}$ accumulation, and significant inhibition of sodium-hydrogen exchanger (NHE) activity. Compared with Neo cells, a single treatment of BI-1 cells with the NHE inhibitor EIPA or siRNA against NHE significantly increased cell death, which suggests that the viability of BI-1 cells is affected by the maintenance of intracellular pH homeostasis through NHE.

• Journal of Nutrition and Health
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• v.38 no.7
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• pp.553-560
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• 2005

The purpose of this study was to examine the lipid peroxidation, plasma antioxidant status and insulin resistance in childhood obesity. To this end, we measured blood lipid profiles, glucose, insulin concentrations, plasma antioxidant vitamins, baseline conjugated diene formation as a measure of LDL oxidation in vivo and TRAP (total radical trapping antioxidant potential) of 93 school children (58 nonobese, 35 overweight-obese). Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). The overweight-obese children showed significantly higher levels of leptin (p < 0.0001) and triglyceride (p < 0.05) and significantly lower level of plasma Iycopene (p < 0.001) and $\gamma$-tocopherol (p < 0.05) compared with the normal weight children. Furthermore, the levels of TRAP were significantly lower in overweight-obese children (p < 0.05). Significant positive relationships between plasma leptin and conjugated dienes formation (p < 0.005) and inverse relationship between plasma leptin and lipid corrected levels of $\beta$-carotene (p < 0.05), Iycopene (p < 0.05) were observed. Our results showed an increased lipid peroxidation and decreased antioxidant capacity in childhood obesity which could be involved in the atherosclerotic process.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.11-21
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• 2021

Adipose tissue secretes many adipokines which contribute to various metabolic processes, such as blood pressure, glucose homeostasis, inflammation and angiogenesis. The biology of adipose tissue in an obese individual is abnormally altered in a manner that increases the body's vulnerability to immune diseases, such as psoriasis. Psoriasis is considered a chronic inflammatory skin disease which is closely associated with being overweight and obese. Additionally, secretion of leptin, a type of adipokine, increases dependently on adipose cell size and adipose accumulation. Likewise, high leptin levels also aggravate obesity via development of leptin resistance, suggesting that leptin and obesity are closely related. Leptin induction in psoriatic patients is mainly driven by the interleukin (IL)-23/helper T (Th) 17 axis pathway. Furthermore, leptin can have an effect on various types of immune cells such as T cells and dendritic cells. Here, we discuss the relationship between obesity and leptin expression as well as the linkage between effect of leptin on immune cells and psoriasis progression.