• 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.

• Clinical and Experimental Pediatrics
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• v.48 no.11
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• pp.1239-1243
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• 2005

Purpose : Iron accumulation interferes with hepatic insulin extraction and affects insulin synthesis and secretion. The purpose of this study is to investigate the correlation between serum ferritin and type 2 diabetes mellitus. Methods : We compared the serum ferritin level among 18 patients in an impaired glucose tolerance (IGT) group, 36 in a type 1 diabetes group, eight in a type 2 diabetes group and 29 in a healthy control group. The correlation between serum ferritin levels and sex, body mass indices(BMI), blood pressure(BP), serum fasting sugar level and serum fasting insulin level were also analyzed. Results : The mean log ferritin were $1.33{\pm}0.32$(healthy control group), $1.63{\pm}0.19$(IGT group) and $1.90{\pm}0.30$(type 2 diabetes group). In the IGT group, log ferritin was higher than in the healthy control group(P=0.001). The log ferritin of the type 2 diabetes group was higher than that of the healthy control group(P=0.001). Comparing log ferritin to other factors, log ferritin had a significant positive correlation with body mass indices(P<0.001), systolic blood pressure(P=0.001), and fasting glucose(P=0.001), fasting insulin(P=0.002). Conclusion : Compared to the normal healthy group, serum ferritin concentrations were significantly higher in the IGT group and the type 2 diabetes group. The elevation of serum ferritin concentration may be a risk factor of type 2 diabetes mellitus.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.415-422
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• 2009

We previously demonstrated that zinc plus arachidonic acid (ZA) treatment lowered blood glucose levels in streptozotocin-induced diabetic rats, genetically diabetic obese (ob/ob) mice, and genetically diabetic, non-obese Goto-Kakizaki rats. However, plasma insulin levels did not increase with ZA treatment, suggesting that ZA lowers blood glucose levels not by stimulating pancreatic insulin secretion. However, it is unclear whether these agents lower blood glucose levels by decreasing hepatic glucose output (HGO) or by increasing glucose utilization in peripheral tissues, or both. In order to determine ZA target organ of insulin action, we divided 18 Sprague-Dawley rats weighing ${\sim}130g$ into 3 groups (6 rats per group) and treated them for four weeks with: (1) Control diet (regular rat chow), (2) High fructose (60.0%) diet only, and (3) the same fructose diet plus zinc (10 mg/L) and arachidonic acid (50 mg/L) containing drinking water. After 4 weeks, insulin action was assessed using the hyperinsulinemic euglycemic clamp technique. Food intake and body weights were comparable in all three groups of rats throughout the study period. Plasma glucose and insulin concentrations, glucose uptake, and HGO in the basal state were all the same in these three rat groups. During the clamp study, fructose-treated and fructose+ZA treated rat groups did not exhibit any detectable change on insulin-mediated glucose uptake compared to controls. High fructose feeding impaired insulin mediated suppression of HGO, compared to controls during clamp (4.39 vs. 2.35 mg/kg/min; p<0.05). However, ZA treatment in high fructose-fed rats showed a remarkable increase in hepatic insulin sensitivity compared to high fructose-fed rats, reflected by a complete recovery in suppression of HGO during the clamp (4.39 vs. 2.18 mg/kg/min; p<0.05). This data suggests that ZA increases insulin sensitivity in liver but not glucose utilization of peripheral tissues in high fructose-fed rats.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.43-54
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• 1982

Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefor, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules. One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile CAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increased in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has teen tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB cAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline. Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30 mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours. The results are summerized as followings. 1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits. 2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid, was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly. 3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile. 4) Only cAMP concentration in bile was significantly increased from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile. 5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile. 6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.57-65
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• 2011

Incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide delay gastric emptying, increasing satiety, and enhance insulin secretion. Two new classes of treatments related to incretin hormones for the management of type 2 diabetes mellitus have emerged: GLP-1 receptor agonists (e.g., exenatide, liraglutide) and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin, vildagliptin, alogliptin), which prevent the degradation of GLP-1. A MEDLINE search was conducted in order to evaluate the efficacy and safety of incretin-based therapies and publications were reviewed. Data from clinical trials indicated incretin-based treatment showed clinically significant reductions in hemoglobin A1c with low risk of hypoglycemia. Weight reductions were observed with GLP-1 receptor agonists where as DPP-4 inhibitors are weight neutral.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.130.3-131
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• 2003

The biological effects of NADPH-dependent isocitrate dehydrogenase (IDPc) inhibitor. DA-11004, was examined in obese zucker rats or streptozotocin-induced diabetic SD rats. Diabetes was induced by injection of streptozotocin (50mg/kg) dissolved in citrate buffer (pH 4.8) into the tail vein and induction of diabetes was confirmed by the measurement of the tail blood glucose level at 48h. DA-11004 (30mg/kg, po) was injected for successive 7days and significantly reduced the plasma glucose in streptozotocin-induced diabetic rats (P<0.05). (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.132.2-133
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• 2003

The biological effects of NADPH-dependent isocitrate dehydrogenase (IDPc) inhibitor, DA-11004, was investigated in obese diabetic (ob/ ob) mice. DA-11004, metformin, and oxalomalate were daily injected (ip) for 8 weeks and after completing an 8-week period of experiment, mice were sacrificed at 1 hr after the last drugs treatment to collect their blood, liver, and adipose tissues(epididymal and retroperitoneal fat). (omitted)

• Sleep Medicine and Psychophysiology
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• v.19 no.1
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• pp.5-10
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• 2012

The release of hormones and the metabolism of human body are controlled by the circadian rhythm related to sleep-wake cycle. Growth hormone, prolactin, thyroid stimulating hormone, cortisol, glucose, and insulin-secretion rates fluctuate according to the sleep-wake cycle. In addition, sleep is related to the appetite regulation and carbohydrate and other energy metabolism. Hypocretin (orexin), an excitatory neuropeptide, regulates waking and diet intake, and the poor sleep increases diet intake. The short sleep duration increases one's body mass index and impairs the function of the endocrine and metabolism, causing increases in the risk of glucose intolerance and diabetes. The poor sleep quality and sleep disorders have similar impact on the metabolic function. In short, the sleep loss and the poor quality of sleep have a detrimental effect on the endocrine and energy metabolism. The improvement of sleep quality by the future research and appropriate clinical treatment would contribute to the decrease of the metabolic diseases such as diabetes.

• Journal of Microbiology and Biotechnology
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• v.14 no.1
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• pp.1-14
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• 2004

More than twenty years have passed since the approval of the first recombinant DNA product for therapeutic use (recombinant human insulin, 1982). However, the biotechnology industry is still facing a shortage of manufacturing capacity due to the increasing demand of therapeutic proteins. This demand has prompted the search for a growing number of biological production systems but, nevertheless, the Gram-negative bacterium Escherichia coli remains one of the most attractive production hosts. This review highlights the most important features and developments of plasmid vector design, emphasizing the different reported strategies for improving the expression and secretion of heterologous proteins using the cellular machinery of E. coli.

• The Korean Journal of Pharmacology
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• v.5 no.2
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• pp.81-86
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• 1969

Alloxan is a diabetogenic agent which destroys the beta-cell of the Langerhan's islet of pancreas and it disturbs the secretion of insulin. It is known that alloxan interfers with the hepatic enzyme activity and some aspect of the other metabolism. The author attempted to investigate the influence of reserpine upon the serum transaminase activity, blood sugar and serum total cholesterol contents of rabbit treated alloxan. The results obtained were summarized as follows; 1. The serum GOT and GPT activity of alloxanized rabbit pretreated with reserpine showed marked decrease compared with alloxan control group. 2. The blood sugar level of alloxanized rabbit pretreated with reserpine showed lower than the alloxan control group. 3. The total cholesterol level of alloxanized rabbit pretreated with reserpine was lower than that of alloxan control group.