Effect of Cholera Toxin Administered Supraspinally or Spinally on the Blood Glucose Level in Pain and D-Glucose Fed Animal Models

Yun-Beom Sim,Soo-Hyun Park,Yu-Jung Kang,Sung-Su Kim,Chea-Ha Kim,Su-Jin Kim,Jun-Sub Jung,Ohk-Hyun Ryu,Moon-Gi Choi,Seong-Soo Choi,Hong-Won Suh 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.2

In the present study, the effect of intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration with cholera toxin (CTX) on the blood glucose level was examined in ICR mice. The i.t. treatment with CTX alone for 24 h dose-dependently increased the blood glucose level. However, i.c.v. treatment with CTX for 24 h did not affect the blood glucose level. When mice were orally fed with D-glucose (2 g/kg), the blood glucose level reached to a maximum level at 30 min and almost returned to the control level at 120 min after D-glucose feeding. I.c.v. pretreatment with CTX increased the blood glucose level in a potentiative manner, whereas i.t. pretreatment with CTX increased the blood glucose level in an additive manner in a D-glucose fed group. In addition, the blood glucose level was increased in formalin-induced pain animal model. I.c.v. pretreatment with CTX enhanced the blood glucose level in a potentiative manner in formalin-induced pain animal model. On the other hand, i.t. pretreatment with CTX increased the blood glucose level in an additive manner in formalin-induced pain animal model. Our results suggest that CTX administered supraspinally or spinally differentially modulates the regulation of the blood glucose level in D-glucose fed model as well as in formalin-induced pain model.

Repaglinide, but Not Nateglinide Administered Supraspinally and Spinally Exerts an Anti-Diabetic Action in D-Glucose Fed and Streptozotocin-Treated Mouse Models

Yun-Beom Sim,Soo-Hyun Park,Yu-Jung Kang,Sung-Su Kim,Chea-Ha Kim,Su-Jin Kim,Su-Min Lim,Jun-Sub Jung,Ohk-Hyun Ryu,Moon-Gi Choi,Hong-Won Suh 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.6

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidi-nediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 μg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

Various pain stimulations cause an increase of the blood glucose level

Sim, Yun-Beom,Park, Soo-Hyun,Kang, Yu-Jung,Jung, Jun-Sub,Ryu, Ohk-Hyun,Choi, Moon-Gi,Suh, Hong-Won The Korean Society for Integrative Biology 2012 Animal cells and systems Vol.16 No.5

The relationship between pain stimulation and the blood glucose level was studied in ICR mice. We examined the possible change of the blood glucose level after the pain stimulation induced by acetic acid injected intraperitoneally (i.p.),, formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and proinflammatory cytokines (TNF-${\alpha}$ and IFN-${\gamma}$) injected intrathecally (i.t.). We found in the present study that acetic acid, formalin, SP, TNF-${\alpha}$, and IFN-${\gamma}$ increased the blood glucose level. The blood glucose level reached at maximal state 30 min and returned to normal level 2 h after the pain stimulation in a fasting group. Furthermore, acetic acid, formalin, SP, TNF-${\alpha}$, and IFN-${\gamma}$ caused the elevation of the blood glucose level in D-glucose-fed group only in an additive manner. However, i.t. injection of glutamate did not alter the blood glucose level in a fasting group. In contrast, i.t. injection of glutamate enhanced the blood glucose level in the D-glucose-fed group. Our results suggest that the blood glucose level appears to be differentially regulated by various pain stimulation induced by acetic acid, formalin, SP, glutamate, and pro-inflammatory cytokines.

Repaglinide, but Not Nateglinide Administered Supraspinally and Spinally Exerts an Anti-Diabetic Action in D-Glucose Fed and Streptozotocin-Treated Mouse Models

Sim, Yun-Beom,Park, Soo-Hyun,Kang, Yu-Jung,Kim, Sung-Su,Kim, Chea-Ha,Kim, Su-Jin,Lim, Su-Min,Jung, Jun-Sub,Ryu, Ohk-Hyun,Choi, Moon-Gi,Suh, Hong-Won The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.6

We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to $30{\mu}g$ of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.

Effect of Cholera Toxin Administered Supraspinally or Spinally on the Blood Glucose Level in Pain and D-Glucose Fed Animal Models

Sim, Yun-Beom,Park, Soo-Hyun,Kang, Yu-Jung,Kim, Sung-Su,Kim, Chea-Ha,Kim, Su-Jin,Jung, Jun-Sub,Ryu, Ohk-Hyun,Choi, Moon-Gi,Choi, Seong-Soo,Suh, Hong-Won The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.2

In the present study, the effect of intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration with cholera toxin (CTX) on the blood glucose level was examined in ICR mice. The i.t. treatment with CTX alone for 24 h dose-dependently increased the blood glucose level. However, i.c.v. treatment with CTX for 24 h did not affect the blood glucose level. When mice were orally fed with D-glucose (2 g/kg), the blood glucose level reached to a maximum level at 30 min and almost returned to the control level at 120 min after D-glucose feeding. I.c.v. pretreatment with CTX increased the blood glucose level in a potentiative manner, whereas i.t. pretreatment with CTX increased the blood glucose level in an additive manner in a D-glucose fed group. In addition, the blood glucose level was increased in formalin-induced pain animal model. I.c.v. pretreatment with CTX enhanced the blood glucose level in a potentiative manner in formalin-induced pain animal model. On the other hand, i.t. pretreatment with CTX increased the blood glucose level in an additive manner in formalin-induced pain animal model. Our results suggest that CTX administered supraspinally or spinally differentially modulates the regulation of the blood glucose level in D-glucose fed model as well as in formalin-induced pain model.

Ghrelin administered spinally increases the blood glucose level in mice

Sim, Yun-Beom,Park, Soo-Hyun,Kim, Sung-Su,Kim, Chea-Ha,Kim, Su-Jin,Lim, Su-Min,Jung, Jun-Sub,Suh, Hong-Won Elsevier 2014 Peptides Vol.54 No.-

<P>Ghrelin is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of ghrelin located in the spinal cord in the regulation of the blood glucose level were investigated in ICR mice. We found that intrathecal (i.t.) injection with ghrelin (from 1 to 10 μg) caused an elevation of the blood glucose level. In addition, i.t. pretreatment with YIL781 (ghrelin receptor antagonist; from 0.1 to 5 μg) markedly attenuated ghrelin-induced hyperglycemic effect. The plasma insulin level was increased by ghrelin. The enhanced plasma insulin level by ghrelin was reduced by i.t. pretreatment with YIL781. However, i.t. pretreatment with glucagon-like peptide-1 (GLP-1; 5 μg) did not affect the ghrelin-induced hyperglycemia. Furthermore, i.t. administration with ghrelin also elevated the blood glucose level, but in an additive manner, in d-glucose-fed model. Our results suggest that the activation of ghrelin receptors located in the spinal cord plays important roles for the elevation of the blood glucose level.</P>

Effect of GABA receptor agonists or antagonists injected spinally on the blood glucose level in mice.

Sim, Yun-Beom,Park, Soo-Hyun,Kang, Yu-Jung,Kim, Sung-Su,Kim, Chea-Ha,Kim, Su-Jin,Jung, Jun-Sub,Ryu, Ohk-Hyun,Choi, Moon-Gi,Suh, Hong-Won Kluwer Academic/Plenum Publishers 2013 Neurochem Res Vol.38 No.5

<P>The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 μg/5 μl) or bicuculline (a GABAA receptor antagonist; 1-10 μg/5 μl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 μg/5 μl) or phaclofen (a GABAB receptor antagonist; 5-10 μg/5 μl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 μg/5 μl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.</P>

The Modulatory Role of Spinally Located Histamine Receptors in the Regulation of the Blood Glucose Level in D-Glucose-Fed Mice

Sim, Yun-Beom,Park, Soo-Hyun,Kim, Sung-Su,Kim, Chea-Ha,Kim, Su-Jin,Lim, Su-Min,Jung, Jun-Sub,Ryu, Ohk-Hyun,Choi, Moon-Gi,Suh, Hong-Won The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (${\alpha}$-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with ${\alpha}$-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, ${\alpha}$-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

The Modulatory Role of Spinally Located Histamine Receptors in the Regulation of the Blood Glucose Level in D-Glucose-Fed Mice

Yun-Beom Sim,Soo-Hyun Park,Sung-Su Kim,Chea-Ha Kim,Su-Jin Kim,Su-Min Lim,Jun-Sub Jung,Ohk-Hyun Ryu,Moon-Gi Choi,Hong-Won Suh 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (car-cinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but sig-nificantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.

임신중 고혈압 산모의 원인 규명을 위한 분자 유전학적 접근: 한국인 Angiotensinogen 유전자 Promoter 부위의 다형성 분석

심순섭 ( Sim Sun Seob ),심재윤 ( Sim Jae Yun ),임준희 ( Im Jun Hui ),박중신 ( Park Jung Sin ),전종관 ( Jeon Jong Gwan ),배광범 ( Bae Gwang Beom ),윤보현 ( Yun Bo Hyeon ),신희철 ( Sin Hui Cheol ) 대한산부인과학회 2003 Obstetrics & Gynecology Science Vol.46 No.8

목적 : 임신중 고혈압 질환의 전반적인 임상 양상을 확인하고 임신중 고혈압 질환의 발생과 angiotensinogen (AGT) 유전자 promoter 부위의 다형성 G(-6)A가 관련되어 있는지를 알아보고자 연구를 시행하였다. 연구 방법 : 1998년 8월부터 2002년 3월까지 임신중 고혈압 질환이 합병된 230명을 대상으로 하였으며, 후향적 의무기록 열람을 하였다. 이들은 새로운 진단기준에 따라 각 군에 배치되었다. 고혈압군은 이완기혈압이 110㎜ Objective : We undertook this study to find out general characteristics of hypertensive disorder in pregnancy and to clarify whether polymorphic marker of promoter region of angiotensinogen G(-6)A polymorphism is associated with the development of hyperte