• The Korean Journal of Physiology
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• v.30 no.2
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• pp.219-229
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• 1996

In order to investigate intra-pancreatic cholinergic roles on insulin action in exocrine secretion, the pancreas was isolated from rats and continuously perfused with modified Krebs-Henseleit solution. Intra-arterial infusion of insulin (100 nM) or cholecystokinin (CCK, 14 pM) alone resulted in stimulation of the volume flow and amylase output. Also insulin potentiated the action of CCK in the exocrine secretion. Tetrodotoxin and atropine completely abolished the potentiating action of insulin and CCK as well as the action of insulin alone, but did not change the action of CCK alone. In order to see an effect of intra-pancreatic neural activation on the insulin action, electrical field stimulation (EFS) with parameters of 20 V, 2 msec and 8 Hz was applied to the isolated pancreas for 10 min under 2.5 or 18 mM glucose background. The EFS voltage-dependently elevated the flow rate and amylase output, and potentiated exocrine secretion in 18 mM glucose infusion compared with 2.5 mM glucose. The potentiating effects of EFS and 18 mM glucose were not observed in the streptozotocin-treated pancreas although it was perfused with 18 mM glucose. However, it was restored when the diabetic pancreas was perfused with porcine insulin(100 nM). Tetrodotoxin and atropine inhibited the pancreatic secretion induced by EFS with the background of 18 mM glucose. The results of present investigation indicate that the intra-pancreatic cholinergic tone exerts a stimulatory influence on the action of insulin in pancreatic exocrine secretion of rats.

• Archives of Pharmacal Research
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• v.21 no.2
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• pp.140-146
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• 1998

Hypoglycemic action of brazilin was found to be based on the improvement of peripheral glucose utility, and this action might be correlated with the insulin action pathway. In the present study we investigated the effect of brazilin on the insulin receptor autophosphorylation, protein kinase C (PKC), protein phosphatase and insulin receptor serine kinase in order to confirm whether the hypoglycemic mechanism is concerned with insulin action pathway. Brazilin was found to inhibit PKC and insulin receptor serine kinase, which are involved in the regulation of insulin signal pathway. But any significant effect was not shown on insulin receptor tyrosine kinase activity, autophosphorylation and phosphatase activity. These findings suggest that brazilin might enhance insulin receptor function by decreasing serine phosphorylation, which might mediate hypoglycemic effect of brazilin.

• The Journal of Korean Medicine
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• v.23 no.1
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• pp.83-91
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• 2002

Objectives : In this study, water extracts from Coix lachryma-jobi Linne var. mayuen Stapf. were investigated for their effects on insulin-like action and glucose uptake in 3T3-Ll cells. Methods : We examined the effects of insulin-like action on the differentiation of 3T3-Ll fibroblasts. The Coicis Semen was treated with hot water and the extract was freeze-dried. The hot water extract was chromatographed on nonionic polymer resin (Amberlite XAD-4, Sigma) with distilled water (Fr. 1), 20% (Fr. 2), 40% (Fr. 3), 60% (Fr. 4), 80% (Fr. 5), and 100% EtOH (Fr. 6), successively. Results : Total extract of Coicis Semen was fractionated into 0 to 100% MeOH with Amberlite XDA-4 column. Treatment of cells with $10{\;}\mu\textrm{g}/ml$ of total extracts of Coicis Semen significantly increased the differentiation (p<0.05). At $1{\;}\mu\textrm{g}/ml$ level of insulin, the differentiation was accelerated (p<0.01). The effect of extracts plus insulin on the differentiation was greater than that of insulin alone. In 3T3-Ll adipocytes, glucose uptake was higher by 2.7 times with 5 uM of total extract in low dosage of insulin (3 ng/ml) than without total extract. 5 and 50 uM of water and 40% MeOH fractions increased glucose uptake by 3.5 times in 3T3-Ll adipocytes (p<0.00l). Conclusions : Coicis Semen contains compounds which playa role of insulin-like action and insulin sensitizer.

• Asian-Australasian Journal of Animal Sciences
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• v.2 no.3
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• pp.218-219
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• 1989

• Molecules and Cells
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• v.38 no.4
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• pp.297-303
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• 2015

Skeletal muscle insulin resistance, which increases the risk for developing various metabolic diseases, including type 2 diabetes, is a common metabolic disorder in obesity and aging. If potential treatments are to be developed to treat insulin resistance, then it is important to fully understand insulin signaling and glucose metabolism. While recent large-scale "omics" studies have revealed the acetylome to be comparable in size to the phosphorylome, the acetylation of insulin signaling proteins and its functional relevance to insulin-stimulated glucose transport and glucose metabolism is not fully understood. In this Mini Review we discuss the acetylation status of proteins involved in the insulin signaling pathway and review their potential effect on, and relevance to, insulin action in skeletal muscle.

• 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.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.329-334
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• 1999

Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity. Thus the understanding of the mechanisms underlying this process at the molecular level may give an insight into the prevention and treatment of these health problems. GLUT4 in rat adipocytes, for example, constantly recycles between the cells surface and an intracellular pool by endocytosis and exocytosis, each of which is regulated by an insulin-sensitive and GLUT4-selective sorting mechanism. Our working hypothesis has been that this sorting mechanism includes a specific interaction of a cytosolic protein with the GLUT4 cytoplasmic domain. Indeed, a synthetic peptide of the C-terminal cytoplasmic domain of GLUT4 induces an insulin-like GLUT4 recruitment when introduced in rat adipocytes. Relevance of these observations to a novel euglycemic drug design is discussed.

• 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.

• Archives of Pharmacal Research
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• v.27 no.4
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• pp.361-370
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• 2004

The discovery of insulin receptor substrate (IRS) proteins and their role to link cell surface receptors to the intracellular signaling cascades is a key step to understanding insulin and insulin-like growth factor (IGF) action. Moreover, IRS-proteins coordinate signals from the insulin and IGF receptor tyrosine kinases with those generated by proinflammatory cytokines and nutrients. The IRS2-branch of the insulin/IGF signaling cascade has an important role in both peripheral insulin response and pancreatic $\beta$-cell growth and function. Dysregulation of IRS2 signaling in mice causes the failure of compensatory hyperinsulinemia during peripheral insulin resistance. IRS protein signaling is down regulated by serine phosphorylation or protea-some-mediated degradation, which might be an important mechanism of insulin resistance during acute injury and infection, or chronic stress associated with aging or obesity. Under-standing the regulation and signaling by IRS1 and IRS2 in cell growth, metabolism and survival will reveal new strategies to prevent or cure diabetes and other metabolic diseases.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.701-707
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• 2007

Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.