• Korean Journal of Biological Psychiatry
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• v.19 no.4
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• pp.187-192
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• 2012

Objectives Although antipsychotic drug clozapine has superior efficacy, this is hampered by metabolic side effects such as weight gain and diabetes. Recent studies demonstrate that clozapine induces insulin resistance. However, the identity and location of insulin resistance induced by clozapine has not been clarified. In this study, the effect of clozapine on central insulin response was investigated in rats. Methods Male Sprague-Dawley rats received intraperitoneal injection of clozapine or vehicle, which was followed by intracerebroventricular injection of insulin or its vehicle. The effects of clozapine on insulin-induced changes in blood glucose level and Akt phosphorylation in hypothalamus were investigated. Results Intraperitoneal injection of clozapine (20 mg/kg) increased blood glucose in rats. Intracerebroventricular injection of insulin reduced blood glucose in rats, which was blunted by pretreatment of clozapine. Accompanied with the antagonistic effect of clozapine to central insulin action in terms of blood glucose, clozapine inhibited the insulin-induced phosphorylation of Akt at Ser473 in rat hypothalamus. Conclusion Administration of clozapine inhibited the central insulin-induced changes in blood glucose and Akt phosphorylation in rat hypothalamus. These findings suggest that hypothalamus could be the site of action for the clozapine-induced insulin resistance.

• Journal of agriculture & life science
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• v.44 no.5
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• pp.65-74
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• 2010

Dairy cow undergoes major adaptations in glucose and lipid metabolism to meet fetal and mammary nutrient requirements during the periparturient period. These adaptations are characterized by major changes in response to the homeostatic signal of insulin. In response to insulin, fatty acids are mobilized to meet energy demand. And cow develop insulin resistance during the late prepartum period to facilitate glucose sparing for the fetus and mammary gland. Insulin resistance is an important adaptation and may be partly responsible for the large increase in plasma nonesterified fatty acid (NEFA) that occurs prior to parturition and coincides with the characteristic decrease in dry matter intake (DMI). Modulation of insulin resistance by administration of thiazolidinedione (TZD) during the periparturient period, likely through the activation of $PPAR{\gamma}$, has substantial potential to minimize energy and immune-related metabolic disorders, and thus may result in increased productivity and improved health of dairy cows.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5315-5320
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• 2016

Purpose: Tumor cell growth and sensitivity to chemotherapy depend on many factors, among which insulin-like growth factors (IGFs) may play important roles. The aim of the present study was to evaluate the levels of insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs) in primary tumors and ascites as predictors of response to neoadjuvant chemotherapy in ovarian cancer (OC) patients. Materials and Methods: Tumor tissue samples and ascitic fluid were obtained from 59 patients with advanced OC. The levels of IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A were determined using ELISA kits. Taking into account the data on expression of these IGF-related proteins and outcome, logistic regression was performed to identify predictors of response to neoajuvant chemotherapy. Results: Human ovarian tumors expressed IGFs, IGFBP-3, IGFBP-4 and PAPP-A and these proteins were also present in ascites fluid and associated with its volume. IGFs and IGFBPs in ascites and soluble PAPP-A might play a key role in ovarian cancer progression. However, levels of proteins of the IGF system in tumors were not significant predictors of objective clinical response (oCR). Univariate analysis showed that the level of IGF-I in ascites was the only independent predictor for oCR. Conclusion: The level of IGF-I in ascites was shown to be an independent predictor of objective clinical response to chemotherapy for OC patients treated with neoadjuvant chemotherapy and debulking surgery.

• YAKHAK HOEJI
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• v.52 no.3
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• pp.182-187
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• 2008

Salicylate (SA) was shown to alleviate insulin resistance. Here, we showed that SA inhibited Ser731 phosphorylation of insulin receptor substrate 1 (IRS1) and S6 kinase activation, and enhanced tyrosine phosphorylation of IRS1 in response to insulin or amino acid. Experiments using a cJun N-terminal kinase (JNK)-deficient cell and an IRS1 JNK-binding mutant showed that JNK is not required for Ser731 phosphorylation. A two-week treatment of obese mice with SA resulted in decreased Ser731 phosphorylation and enhanced insulin signaling. These results suggest that SA enhances insulin signaling by inhibiting Ser731 phosphorylation of IRS1.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.185-197
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• 2004

Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes (6). To explore the mechanism underlying this effect, we have used the 3T3-Ll adipocytes as a cell type which would represent the periphery, in vivo. Exposure of 3T3-Ll adipocytes to chronic insulin leads to the a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to fibroin blocked, in part, the response to chronic insulin but also increased the sensitivity of control cells to the acute action of insulin. The later effect was most robust at physiological concentrations of insulin. Fibroin did not prevent the insulin-induced down-regulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no affect on the loss in activity of the insulin-sensitive down-stream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin up-regulated GLUT1 which increased its expression at the cell surface and caused the redistribution of GLUT4 to the plasma membrane. Together, these later effects would lead to an improvement in hyperglycemia in vivo which would in turn reduce the need for insulin.

• Asian-Australasian Journal of Animal Sciences
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• v.2 no.3
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• pp.249-250
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• 1989

• Asian-Australasian Journal of Animal Sciences
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• v.2 no.3
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• pp.222-223
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• 1989

• Asian-Australasian Journal of Animal Sciences
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• v.2 no.3
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• pp.216-217
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• 1989

• Asian-Australasian Journal of Animal Sciences
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• v.10 no.1
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• pp.134-140
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• 1997

Objectives of this study were to determine effects of insulin on acetyl-CoA carboxylase (ACC) activity and correlate this activity with relative amounts of ACC in MAC-T cells. MAC-T cells were grown in Medium 199 supplemented with fetal bovine serum (5%), cortisol ($1{\mu}g/ml$), and insulin ($1{\mu}g/ml$). At confuluence, the cells were transferred to $100mm^2$ culture dishes coated with the extracelluar matrix. After 10 h of incubation, the media were replaced with media without fetal bovine serum and the concentration of insulin was lowered to 5 ng/ml. After 24 h, the media were changed to contain the varying concentrations of insulin and incubations continued for 48 h. The addition of insulin resulted in increases in the specific activity of ACC. The maximal effects of insulin on the ACC activity occurred at concentrations of insulin, 1,000 ng/ml. In contrast, the relative change in lactate dehydrogenase (LDH) activity in response to increasing insulin concentration was minimal as compared to the effects of insulin on ACC. Transblot and enhanced chemiluminescence (ECL) analysis indicated that the increase in ACC activity in MAC-T cells caused by insulin were due to actual increases in amounts of enzyme.

• The Korean Journal of Zoology
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• v.38 no.3
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• pp.426-432
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• 1995

Expression of $\beta$-lactoglobulin gene in mammary tissue is strongly induced by lactogenic hormones such as prolactin, glucocorticoid, and insulin. In order to elucidate the regulatory mechanism underlying such hormonal induction, the response of the caprine $\beta$-lactoglobulin gene promoter to lactogenic hormones was analyzed in cultured HC11 mammary cells. Expression with serial deletions of the 5' -regulatory sequence of the $\beta$-lactoglobulin promoter revealed that two regions are responsible for a substantial change in hormonal indudbility. The region upstream of-1692, which exhibited strong repression of the downstream promoter, mediated the induction by insulin. This insulin-response was independent of the other two lactogenic hormones, prolactin and glucocorticoid. The other region from -740 to -470, which showed strong activation of the $\beta$-lactoglobulin promoter in confluent HC11 mammary cells, mediated mainly the response to a glucocorticoid analogue, dexametasone. The induction by the latter region, however, was suppressed by the usptream repression without insulin treatment. These results suggest that the induction of $\beta$-lactoglobulin promoter activity by lactogenic hormones in mammary cells may be achieved by the combined action of derepression by in sulin and activation by glucocorticoid and prolactin. Dexametasone response by the latter region seems to be mediated by the glucocorticoid receptor site around -7OObp.